Search results for: pharmaceutical molecules

Authors: N. Rajendra Prasad

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Resveratrol (RSV), a grape phytochemical, has drawn greater attention because of its beneficial ef-fects against cancer. However, RSV has some draw-backs such as unstabilization, poor water solubility and short biological half time, which limit the utili-zation of RSV in medicine, food and pharmaceutical industries. In this study, we have encapsulated RSV in gelatin nanoparticles (GNPs) and studied its anti-cancer efficacy in NCI-H460 lung cancer cells. SEM and DLS studies have revealed that the prepared RSV-GNPs possess spherical shape with a mean diameter of 294 nm. The successful encapsulation of RSV in GNPs has been achieved by the cross-linker glutaraldehyde probably through Schiff base reaction and hydrogen bond interaction. Spectrophotometric analysis revealed that the max-imum of 93.6% of RSV has been entrapped in GNPs. In vitro drug release kinetics indicated that there was an initial burst release followed by a slow and sustained release of RSV from GNPs. The prepared RSV-GNPs exhibited very rapid and more efficient cellular uptake than free RSV. Further, RSV-GNPs treatment showed greater antiproliferative efficacy than free RSV treatment in NCI-H460 cells. It has been found that greater ROS generation, DNA damage and apoptotic incidence in RSV-GNPs treated cells than free RSV treatment. Erythrocyte aggregation assay showed that the prepared RSV-GNPs formulation elicit no toxic response. HPLC analysis revealed that RSV-GNPs was more bioavailable and had a longer half-life than free RSV. Hence, GNPs carrier system might be a promising mode for controlled delivery and for improved therapeutic index of poorly water soluble RSV.

Keywords: resveratrol, coacervation, anticancer gelatin nanoparticles, lung cancer, controlled release

Procedia PDF Downloads 429

Authors: Srinivas Bathini, Duraichelvan Raju, Simona Badilescu, Muthukumaran Packirisamy

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A bio-sensing method, based on the plasmonic property of gold nano-islands, has been developed for detection of exosomes in a clinical setting. The position of the gold plasmon band in the UV-Visible spectrum depends on the size and shape of gold nanoparticles as well as on the surrounding environment. By adsorbing various chemical entities, or binding them, the gold plasmon band will shift toward longer wavelengths and the shift is proportional to the concentration. Exosomes transport cargoes of molecules and genetic materials to proximal and distal cells. Presently, the standard method for their isolation and quantification from body fluids is by ultracentrifugation, not a practical method to be implemented in a clinical setting. Thus, a versatile and cutting-edge platform is required to selectively detect and isolate exosomes for further analysis at clinical level. The new sensing protocol, instead of antibodies, makes use of a specially synthesized polypeptide (Vn96), to capture and quantify the exosomes from different media, by binding the heat shock proteins from exosomes. The protocol has been established and optimized by using a glass substrate, in order to facilitate the next stage, namely the transfer of the protocol to a microfluidic environment. After each step of the protocol, the UV-Vis spectrum was recorded and the position of gold Localized Surface Plasmon Resonance (LSPR) band was measured. The sensing process was modelled, taking into account the characteristics of the nano-island structure, prepared by thermal convection and annealing. The optimal molar ratios of the most important chemical entities, involved in the detection of exosomes were calculated as well. Indeed, it was found that the results of the sensing process depend on the two major steps: the molar ratios of streptavidin to biotin-PEG-Vn96 and, the final step, the capture of exosomes by the biotin-PEG-Vn96 complex. The microfluidic device designed for sensing of exosomes consists of a glass substrate, sealed by a PDMS layer that contains the channel and a collecting chamber. In the device, the solutions of linker, cross-linker, etc., are pumped over the gold nano-islands and an Ocean Optics spectrometer is used to measure the position of the Au plasmon band at each step of the sensing. The experiments have shown that the shift of the Au LSPR band is proportional to the concentration of exosomes and, thereby, exosomes can be accurately quantified. An important advantage of the method is the ability to discriminate between exosomes having different origins.

Keywords: exosomes, gold nano-islands, microfluidics, plasmonic biosensing

Procedia PDF Downloads 151

Authors: Chrislaura Carmo, Luca Deiana, Mafalda Laranjo, Abilio Sobral, Armando Cordova

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Photodynamic therapy (PDT) is currently used for the treatment of malignancies and premalignant tumors. It is based on the capture of a photosensitizing molecule (PS) which, when excited by light at a certain wavelength, reacts with oxygen and generates oxidizing species (radicals, singlet oxygen, triplet species) in target tissues, leading to cell death. BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indaceno) derivatives are emerging as important candidates for photosensitizer in photodynamic therapy of cancer cells due to their high triplet quantum yield. Today these dyes are relevant molecules in photovoltaic materials and fluorescent sensors. In this study, it will be demonstrated the possibility that BODIPY can be covalently linked to thioglycolic acid through the click reaction. Thiol−ene click chemistry has become a powerful synthesis method in materials science and surface modification. The design of biobased allyl-terminated precursors with high renewable carbon content for the construction of the thiol-ene polymer networks is essential for sustainable development and green chemistry. The work aims to synthesize the BODIPY (10-(4-(allyloxy) phenyl)-2,8-diethyl-5,5-difluoro-1,3,7,9-tetramethyl-5H-dipyrrolo[1,2-c:2',1'-f] [1,3,2] diazaborinin-4-ium-5-uide) and to click reaction with Thioglycolic acid. BODIPY was synthesized by the condensation reaction between aldehyde and pyrrole in dichloromethane, followed by in situ complexation with BF3·OEt2 in the presence of the base. Then it was functionalized with allyl bromide to achieve the double bond and thus be able to carry out the click reaction. The thiol−ene click was performed using DMPA (2,2-Dimethoxy-2-phenylacetophenone) as a photo-initiator in the presence of UV light (320–500 nm) in DMF at room temperature for 24 hours. Compounds were characterized by standard analytical techniques, including UV-Vis Spectroscopy, 1H, 13C, 19F NMR and mass spectroscopy. The results of this study will be important to link BODIPY to polymers through the thiol group offering a diversity of applications and functionalization. This new molecule can be tested as third-generation photosensitizers, in which the dye is targeted by antibodies or nanocarriers by cells, mainly in cancer cells, PDT and Photodynamic Antimicrobial Chemotherapy (PACT). According to our studies, it was possible to visualize a click reaction between allyl BODIPY and thioglycolic acid. Our team will also test the reaction with other thiol groups for comparison. Further, we will do the click reaction of BODIPY with a natural polymer linked with a thiol group. The results of the above compounds will be tested in PDT assays on various lung cancer cell lines.

Keywords: bodipy, click reaction, thioglycolic acid, allyl, thiol-ene click

Procedia PDF Downloads 107

Authors: Yunjia Yang, Peng Li, Gordon Xu, Timothy Mahony, Bing Zhang, Neena Mitter, Karishma Mody

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Sheep flystrike is one of the most economically important diseases affecting the Australian sheep and wool industry (>356M/annually). Currently, control of Lucillia cuprina relies almost exclusively on chemicals controls, and the parasite has developed resistance to nearly all control chemicals used in the past. It is, therefore, critical to develop an alternative solution for the sustainable control and management of flystrike. RNA interference (RNAi) technologies have been successfully explored in multiple animal industries for developing parasites controls. This research project aims to develop a RNAi based biological control for sheep blowfly. Double-stranded RNA (dsRNA) has already proven successful against viruses, fungi, and insects. However, the environmental instability of dsRNA is a major bottleneck for successful RNAi. Bentonite polymer (BenPol) technology can overcome this problem, as it can be tuned for the controlled release of dsRNA in the gut challenging pH environment of the blowfly larvae, prolonging its exposure time to and uptake by target cells. To investigate the potential of BenPol technology for dsRNA delivery, four different BenPol carriers were tested for their dsRNA loading capabilities, and three of them were found to be capable of affording dsRNA stability under multiple temperatures (4°C, 22°C, 40°C, 55°C) in sheep serum. Based on stability results, dsRNA from potential targeted genes was loaded onto BenPol carriers and tested in larvae feeding assays, three genes resulting in knockdowns. Meanwhile, a primary blowfly embryo cell line (BFEC) derived from L. cuprina embryos was successfully established, aim for an effective insect cell model for testing RNAi efficacy for preliminary assessments and screening. The results of this study establish that the dsRNA is stable when loaded on BenPol particles, unlike naked dsRNA rapidly degraded in sheep serum. The stable nanoparticle delivery system offered by BenPol technology can protect and increase the inherent stability of dsRNA molecules at higher temperatures in a complex biological fluid like serum, providing promise for its future use in enhancing animal protection.

Keywords: lucilia cuprina, primary cell line establishment, RNA interference, insect cell transfection

Procedia PDF Downloads 54

Authors: M. Nita-Lazar, E. Manea, C. Bumbac, A. Banciu, C. Stoica

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The population and economic growth have generated a significant new number of pollutant compounds which have to be degraded before reaching the environment. The wastewater treatment plants (WWTPs) have been the last barrier between the domestic and/or industrial wastewaters and the environment. At present, the conventional WWTPs have very high operational costs, most of them linked to the aeration process (60-65% from total energy costs related to wastewater treatment). In addition, they have had a low efficiency in pollutants removal such as pharmaceutical and other resilient anthropogenic compounds. In our study, we have been focused on new wastewater treatment strategies to enhance the efficiency of pollutants removal and decrease the wastewater treatment operational costs. The usage of mixed microalgae-bacteria granules technology generated high efficiency and low costs by a better harvesting and less expensive aeration. The intertrophic relationships between microalgae and bacteria have been characterized by the structure of the population community to their metabolic relationships. The results, obtained by microscopic studies, showed well-organized and stratified microalgae-bacteria granules where bacteria have been enveloped in the microalgal structures. Moreover, their population community structure has been modulated as well as their nitrification, denitrification processes (analysis based on qPCR genes expression) by the type of the pollutant compounds and amounts. In conclusion, the understanding and modulation of intertrophic relationships between microalgae and bacteria could be an economical and technological viable alternative to the conventional wastewater treatment. Acknowledgements: This research was supported by grant PN-III-P4-ID-PCE-2016-0865 from the Romanian National Authority for Scientific Research and Innovation CNCS/CCCDI-UEFISCDI.

Keywords: activated sludge, bacteria, granules, microalgae

Procedia PDF Downloads 99

Authors: Aleksandra Łochowicz, Daria Świętochowska, Loredano Pollegioni, Nazim Ocal, Franck Charmantray, Laurence Hecquet, Katarzyna Szymańska

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Multienzymatic cascade reactions are nowadays widely used in pharmaceutical, chemical and cosmetics industries to produce high valuable compounds. They can be carried out in two ways, step by step and one-pot. If two or more enzymes are in the same reaction vessel is necessary to work out the compromise to run the reaction in optimal conditions for each enzyme. So far most of the reports of multienzymatic cascades concern on usage of free enzymes. Unfortunately using free enzymes as catalysts of reactions accomplish high cost. What is more, free enzymes are soluble in solvents which makes reuse impossible. To overcome this obstacle enzymes can be immobilized what provides heterogeneity of biocatalyst that enables reuse and easy separation of the enzyme from solvents and reaction products. Usually, immobilization increase also the thermal and operational stability of enzyme. The advantages of using immobilized multienzymes are enhanced enzyme stability, improved cascade enzymatic activity via substrate channeling, and ease of recovery for reuse. The one-pot immobilized multienzymatic cascade can be carried out in mixed or coimmobilized type. When biocatalysts are coimmobilized on the same carrier the are in close contact to each other which increase the reaction rate and catalytic efficiency, and eliminate the lag time. However, in this type providing the optimal conditions both in the process of immobilization and cascade reaction for each enzyme is complicated. Herein, we examined immobilization of 3 enzymes: D-amino acid oxidase from Rhodotorula gracilis, commercially available catalase and transketolase from Geobacillus stearothermophilus. As a support we used silica monoliths with hierarchical structure of pores. Then we checked their stability and reusability in one-pot cascade of L-erythrulose and hydroxypuryvate acid synthesis.

Keywords: biocatalysts, enzyme immobilization, multienzymatic reaction, silica carriers

Procedia PDF Downloads 130

Authors: Sujatha Edla

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Introduction: New compounds and possible uses for the bioactive substances produced by freshwater cyanobacteria are constantly being discovered through research. Certain molecules are hazardous to the environment and human health, but others have potential applications in industry, biotechnology, and pharmaceuticals. These discoveries advance our knowledge of the varied functions these microbes perform in different ecosystems. Cyanobacterial silver nanoparticles (AgNPs) have special qualities and possible therapeutic advantages, which make them very promising for a range of medicinal uses. Aim: In our study; the attention was focused on the analysis and characterization of bioactive compounds extracted from freshwater cyanobacteria Planktothricoides raciorskii and its comparative study on Cyanobacteria-mediated silver nanoparticles synthesized by cell-free extract of Planktothricoides raciorskii. Material and Methods: A variety of bioactive secondary metabolites have been extracted, purified, and identified from cyanobacterial species using column chromatography, FTIR, and GC-MS/MS chromatography techniques and evaluated for antibacterial and cytotoxic studies, where the Cyanobacterial silver nanoparticles (CSNPs) were characterized by UV-Vis spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) analysis and were further tested for antibacterial and cytotoxic efficiency. Results: The synthesis of CSNPs was confirmed through visible color change and shift of peaks at 430–445 nm by UV-Vis spectroscopy. The size of CSNPs was between 22 and 34 nm and oval-shaped which were confirmed by SEM and TEM analyses. The FTIR spectra showed a new peak at the range of 3,400–3,460 cm−1 compared to the control, confirming the reduction of silver nitrate. The antibacterial activity of both crude bioactive compound extract and CSNPs showed remarkable activity with Zone of inhibition against E. coli with 9.5mm and 10.2mm, 13mm and 14.5mm against S. paratyphi, 9.2mm and 9.8mm zone of inhibition against K. pneumonia by both crude extract and CSNPs, respectively. The cytotoxicity as evaluated by extracts of Planktothricoides raciorskii against MCF7-Human Breast Adenocarcinoma cell line and HepG2- Human Hepatocellular Carcinoma cell line employing MTT assay gave IC50 value of 47.18ug/ml, 110.81ug/ml against MCF7cell line and HepG2 cell line, respectively. The cytotoxic evaluation of Planktothricoides raciorskii CSNPs against the MCF7cell line was 43.37 ug/ml and 20.88 ug/ml against the HepG2 cell line. Our ongoing research in this field aims to uncover the full therapeutic potential of cyanobacterial silver nanoparticles and address any associated challenges.

Keywords: cyanobacteria, silvernanoparticles, pharmaceuticals, bioactive compounds, cytotoxic

Procedia PDF Downloads 39

Authors: Matthew E. Potter, Daniel J. Stewart, Lindsay M. Armstrong, Pier J. A. Sazio, Robert R. Raja

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Rising CO₂ levels in the atmosphere means that CO₂ is a highly desirable feedstock. This requires specific catalysts to be designed to activate this inert molecule, combining a catalytic site tailored for CO₂ transformations with a support that can readily adsorb CO₂. Metal organic frameworks (MOFs) are regularly used as CO₂ sorbents. The organic nature of the linker molecules, connecting the metal nodes, offers many post-synthesis modifications to introduce catalytic active sites into the frameworks. However, the metal nodes may be coordinatively unsaturated, allowing them to bind to organic moieties. Imidazoles have shown promise catalyzing the formation of cyclic carbonates from epoxides with CO₂. Typically, this synthesis route employs toxic reagents such as phosgene, liberating HCl. Therefore an alternative route with CO₂ is highly appealing. In this work we design active sites for CO₂ activation, by tethering substituted-imidazole organocatalytic species to the available Cr3+ metal nodes of a Cr-MIL-101 MOF, for the first time, to create a tailored species for carbon capture utilization applications. Our tailored design strategy combining a CO₂ sorbent, Cr-MIL-101, with an anchored imidazole results in a highly active and selective multifunctional catalyst, achieving turnover frequencies of over 750 hr-1. These findings demonstrate the synergy between the MOF framework and imidazoles for CO₂ utilization applications. Further, the effect of substrate variation has been explored yielding mechanistic insights into this process. Through characterization, we show that the structural and compositional integrity of the Cr-MIL-101 has been preserved on functionalizing the imidazoles. Further, we show the binding of the imidazoles to the Cr3+ metal nodes. This can be seen through our EPR study, where the distortion of the Cr3+ on binding to the imidazole shows the CO₂ binding site is close to the active imidazole. This has a synergistic effect, improving catalytic performance. We believe the combination of MOF support and organocatalyst allows many possibilities to generate new multifunctional catalysts for CO₂ utilisation. In conclusion, we have validated our design procedure, combining a known CO₂ sorbent, with an active imidazole species to create a unique tailored multifunctional catalyst for CO₂ utilization. This species achieves high activity and selectivity for the formation of cyclic carbonates and offers a sustainable alternative to traditional synthesis methods. This work represents a unique design strategy for CO₂ utilization while offering exciting possibilities for further work in characterization, computational modelling, and post-synthesis modification.

Keywords: carbonate, catalysis, MOF, utilisation

Procedia PDF Downloads 158

Authors: Aloke Bapli, Debabrata Seth

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Graphene oxide (GO) is the two-dimensional (2D) nanoscale allotrope of carbon having several physiochemical properties such as high mechanical strength, high surface area, strong thermal and electrical conductivity makes it an important candidate in various modern applications such as drug delivery, supercapacitors, sensors etc. GO has been used in the photothermal treatment of cancers and Alzheimer’s disease etc. The main idea to choose GO in our work is that it is a surface active molecule, it has a large number of hydrophilic functional groups such as carboxylic acid, hydroxyl, epoxide on its surface and in basal plane. So it can easily interact with organic fluorophores through hydrogen bonding or any other kind of interaction and easily modulate the photophysics of the probe molecules. We have used different spectroscopic techniques for our work. The Ground-state absorption spectra and steady-state fluorescence emission spectra were measured by using UV-Vis spectrophotometer from Shimadzu (model-UV-2550) and spectrofluorometer from Horiba Jobin Yvon (model-Fluoromax 4P) respectively. All the fluorescence lifetime and anisotropy decays were collected by using time-correlated single photon counting (TCSPC) setup from Edinburgh instrument (model: LifeSpec-II, U.K.). Herein, we described the photophysics of a hydrophilic molecule 7-(n,n׀-diethylamino) coumarin-3-carboxylic acid (7-DCCA) in the reverse micelles containing GO. It was observed that photophysics of dye is modulated in the presence of GO compared to photophysics of dye in the absence of GO inside the reverse micelles. Here we have reported the solvent relaxation and rotational relaxation time in GO containing reverse micelle and compare our work with normal reverse micelle system by using 7-DCCA molecule. Normal reverse micelle means reverse micelle in the absence of GO. The absorption maxima of 7-DCCA were blue shifted and emission maxima were red shifted in GO containing reverse micelle compared to normal reverse micelle. The rotational relaxation time in GO containing reverse micelle is always faster compare to normal reverse micelle. Solvent relaxation time, at lower w₀ values, is always slower in GO containing reverse micelle compare to normal reverse micelle and at higher w₀ solvent relaxation time of GO containing reverse micelle becomes almost equal to normal reverse micelle. Here emission maximum of 7-DCCA exhibit bathochromic shift in GO containing reverse micelles compared to that in normal reverse micelles because in presence of GO the polarity of the system increases, as polarity increases the emission maxima was red shifted an average decay time of GO containing reverse micelle is less than that of the normal reverse micelle. In GO containing reverse micelle quantum yield, decay time, rotational relaxation time, solvent relaxation time at λₑₓ=375 nm is always higher than λₑₓ=405 nm, shows the excitation wavelength dependent photophysics of 7-DCCA in GO containing reverse micelles.

Keywords: photophysics, reverse micelle, rotational relaxation, solvent relaxation

Procedia PDF Downloads 136

Authors: Sameen Tariq, Saira Bano, Sayyada Ghufrana Nadeem

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The Ocean, which covers over 70% of the world's surface, is wealthy in biodiversity as well as a rich wellspring of microorganisms with huge potential. The oceanic climate is home to an expansive scope of plants, creatures, and microorganisms. Marine microbial networks, which incorporate microscopic organisms, infections, and different microorganisms, enjoy different benefits in biotechnological processes. Samples were collected from marine environments, including soil and water samples, to cultivate the uncultured marine organisms by using Zobell’s medium, Sabouraud’s dextrose agar, and casein media for this purpose. Following isolation, we conduct microscopy and biochemical tests, including gelatin, starch, glucose, casein, catalase, and carbohydrate hydrolysis for further identification. The results show that more gram-positive and gram-negative bacteria. The isolation process of marine organisms is essential for understanding their ecological roles, unraveling their biological secrets, and harnessing their potential for various applications. Marine organisms exhibit remarkable adaptations to thrive in the diverse and challenging marine environment, offering vast potential for scientific, medical, and industrial applications. The isolation process plays a crucial role in unlocking the secrets of marine organisms, understanding their biological functions, and harnessing their valuable properties. They offer a rich source of bioactive compounds with pharmaceutical potential, including antibiotics, anticancer agents, and novel therapeutics. This study is an attempt to explore the diversity and dynamics related to marine microflora and their role in biofilm formation.

Keywords: marine microorganisms, ecosystem, fungi, biofilm, gram-positive, gram-negative

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Authors: Thi Huong Vu, Vijay Jayasena, Zhongxiang Fang, Gary Dykes

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Carob kibble has recently received attention due to the presence of high level of polyphenol antioxidants. The capacity of microorganisms to improve antioxidant activities and total phenolics in carob kibble was investigated in the study. Two types of microorganisms including lactic acid bacteria Lactobacillus plantarum (L. plantarum) and yeast Saccharomyces cerevisiae (S. cerevisiae) were used in single and in their combination as starters. The total phenolic content was determined by the Folin–Ciocalteu method. Antioxidant activities were assessed scavenging capacity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS). The study found that S. cerevisiae alone considerably improved 55% total phenolics content at 15 h, while L. plantarum caused in a loss of 20% through the process. Antioxidant capacity of the yeast-fermented samples significantly increased by 43 % and 10 % in ABTS and DPPH assays, respectively. However, reduction of 13 % and 32 % inhibition were recorded in the carob treated with L. plantarum. In the combination of S. cerevisiae and L. plantarum (1:1), both total phenolic content and antioxidant activity of carob kibble were a similar trend as these of S. cerevisiae single, but a lower improvement. The antioxidant power of the extracts was linearly correlated to their total phenolic contents (R=0.75). The results suggested that S. cerevisiae alone was the better for enhancement of both total phenolic content and antioxidant activity in carob kibble using submerged fermentation. The efficiency of fermentation reached the highest at 15h. Thus submerged fermentation with S. cerevisiae offers a tool with simple and cost effective to further increase the bioactive potential of carob kibble, which is in use for food, cosmetic and pharmaceutical industries.

Keywords: antioxidant activity, carob kibble, lactobacillus plantarum, saccharomyces cerevisiae, total phenolics

Procedia PDF Downloads 267

Authors: Bao-Fang Wen, Meng-Na Dai, Gao-Pei Zhu, Chen-Xi Zhang, Jing Sun, Xun-Bao Yin, Yu-Han Zhao, Hong-Wei Sun, Wei-Fen Zhang

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A drug-loaded nanoparticles containing berberine hydrochloride (BH/FA-CTS-NPs) was prepared. The physicochemical characterizations of BH/FA-CTS-NPs and the inhibitory effect on the HeLa cells were investigated. Folic acid-conjugated chitosan (FA-CTS) was prepared by amino reaction of folic acid active ester and chitosan molecules; BH/FA-CTS-NPs were prepared using ionic cross-linking technique with BH as a model drug. The morphology and particle size were determined by Transmission Electron Microscope (TEM). The average diameters and polydispersity index (PDI) were evaluated by Dynamic Light Scattering (DLS). The interaction between various components and the nanocomplex were characterized by Fourier Transform Infrared Spectroscopy (FT-IR). The entrapment efficiency (EE), drug-loading (DL) and in vitro release were studied by UV spectrophotometer. The effect of cell anti-migratory and anti-invasive actions of BH/FA-CTS-NPs were investigated using MTT assays, wound healing assays, Annexin-V-FITC single staining assays, and flow cytometry, respectively. HeLa nude mice subcutaneously transplanted tumor model was established and treated with different drugs to observe the effect of BH/FA-CTS-NPs in vivo on HeLa bearing tumor. The BH/FA-CTS-NPs prepared in this experiment have a regular shape, uniform particle size, and no aggregation phenomenon. The results of DLS showed that mean particle size, PDI and Zeta potential of BH/FA-CTS NPs were (249.2 ± 3.6) nm, 0.129 ± 0.09, 33.6 ± 2.09, respectively, and the average diameter and PDI were stable in 90 days. The results of FT-IR demonstrated that the characteristic peaks of FA-CTS and BH/FA-CTS-NPs confirmed that FA-CTS cross-linked successfully and BH was encapsulated in NPs. The EE and DL amount were (79.3 ± 3.12) % and (7.24 ± 1.41) %, respectively. The results of in vitro release study indicated that the cumulative release of BH/FA-CTS NPs was (89.48±2.81) % in phosphate-buffered saline (PBS, pH 7.4) within 48h; these results by MTT assays and wund healing assays indicated that BH/FA-CTS NPs not only inhibited the proliferation of HeLa cells in a concentration and time-dependent manner but can induce apoptosis as well. The subcutaneous xenograft tumor formation rate of human cervical cancer cell line HeLa in nude mice was 98% after inoculation for 2 weeks. Compared with BH group and BH/CTS-NPs group, the xenograft tumor growth of BH/FA-CTS-NPs group was obviously slower; the result indicated that BH/FA-CTS-NPs could significantly inhibit the growth of HeLa xenograft tumor. BH/FA-CTS NPs with the sustained release effect could be prepared successfully by the ionic crosslinking method. Considering these properties, block proliferation and impairing the migration of the HeLa cell line, BH/FA-CTS NPs could be an important compound for consideration in the treatment of cervical cancer.

Keywords: folic-acid, chitosan, berberine hydrochloride, nanoparticles, cervical cancer

Procedia PDF Downloads 102

Authors: P. Acosta-Santamaría, A. Ibatá-Soto, A. López-Vásquez

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Organic compounds in wastewaters coming from textile and pharmaceutical industry generated multiple harmful effects on the environment and the human health. One of them is the methyl orange (MeO), an azoic dye considered to be a recalcitrant compound. The heterogeneous photocatalysis emerges as an alternative for treating this type of hazardous compounds, through the generation of OH radicals using radiation and a semiconductor oxide. According to the author’s knowledge, catalysts such as TiO₂ doped with metals show high efficiency in degrading MeO; however, this presents economic limitations on industrial scale. Black sand can be considered as a naturally doped catalyst because in its structure is common to find compounds such as titanium, iron and aluminum oxides, also elements such as zircon, cadmium, manganese, etc. This study reports the photocatalytic activity of the mineral black sand used as semiconductor in the discoloration of MeO by oxidation and reduction photocatalytic techniques. For this, magnetic composites from the mineral were prepared (RM, M1, M2 and NM) and their activity were tested through MeO discoloration while TiO₂ was used as reference. For the fractions, chemical, morphological and structural characterizations were performed using Scanning Electron Microscopy with Energy Dispersive X-Ray (SEM-EDX), X-Ray Diffraction (XRD) and X-Ray Fluorescence (XRF) analysis. M2 fraction showed higher MeO discoloration (93%) in oxidation conditions at pH 2 and it could be due to the presence of ferric oxides. However, the best result to reduction process was using M1 fraction (20%) at pH 2, which contains a higher titanium percentage. In the first process, hydrogen peroxide (H₂O₂) was used as electron donor agent. According to the results, black sand mineral can be used as natural semiconductor in photocatalytic process. It could be considered as a photocatalyst precursor in such processes, due to its low cost and easy access.

Keywords: black sand mineral, methyl orange, oxidation, photocatalysis, reduction

Procedia PDF Downloads 361

Authors: Jigar N. Shah, Hiral J. Shah, Praful D. Bharadia

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The major challenge faced by formulation scientists in transdermal drug delivery system is to overcome the inherent barriers related to skin permeation. The stratum corneum layer of the skin is working as the rate limiting step in transdermal transport and reduce drug permeation through skin. Many approaches have been used to enhance the penetration of drugs through this layer of the skin. The purpose of this study is to investigate the development and evaluation of a combined approach of drug carriers and iontophoresis as a vehicle to improve skin permeation of an analgesic drug. Iontophoresis is a non-invasive technique for transporting charged molecules into and through tissues by a mild electric field. It has been shown to effectively deliver a variety of drugs across the skin to the underlying tissue. In addition to the enhanced continuous transport, iontophoresis allows dose titration by adjusting the electric field, which makes personalized dosing feasible. Drug carrier could modify the physicochemical properties of the encapsulated molecule and offer a means to facilitate the percutaneous delivery of difficult-to-uptake substances. Recently, there are some reports about using liposomes, microemulsions and polymeric nanoparticles as vehicles for iontophoretic drug delivery. Niosomes, the nonionic surfactant-based vesicles that are essentially similar in properties to liposomes have been proposed as an alternative to liposomes. Niosomes are more stable and free from other shortcoming of liposomes. Recently, the transdermal delivery of certain drugs using niosomes has been envisaged and niosomes have proved to be superior transdermal nanocarriers. Proniosomes overcome some of the physical stability related problems of niosomes. The proniosomal structure was liquid crystalline-compact niosomes hybrid which could be converted into niosomes upon hydration. The combined use of drug carriers and iontophoresis could offer many additional benefits. The system was evaluated for Encapsulation Efficiency, vesicle size, zeta potential, Transmission Electron Microscopy (TEM), DSC, in-vitro release, ex-vivo permeation across skin and rate of hydration. The use of proniosomal gel as a vehicle for the transdermal iontophoretic delivery was evaluated in-vitro. The characteristics of the applied electric current, such as density, type, frequency, and on/off interval ratio were observed. The study confirms the synergistic effect of proniosomes and iontophoresis in improving the transdermal permeation profile of selected analgesic drug. It is concluded that proniosomal gel can be used as a vehicle for transdermal iontophoretic drug delivery under suitable electric conditions.

Keywords: iontophoresis, niosomes, permeation enhancement, transdermal delivery

Procedia PDF Downloads 357

Authors: Sulalit Bandyopadhyay, Muhammad Awais Ashfaq Alvi, Anuvansh Sharma, Wilhelm R. Glomm

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Release of drugs from nanogels and nanogel-based systems can occur under the influence of external stimuli like temperature, pH, magnetic fields and so on. pNIPAm-AAc nanogels respond to the combined action of both temperature and pH, the former being mostly determined by hydrophilic-to-hydrophobic transitions above the volume phase transition temperature (VPTT), while the latter is controlled by the degree of protonation of the carboxylic acid groups. These nanogels based systems are promising candidates in the field of drug delivery. Combining nanogels with magneto-plasmonic nanoparticles (NPs) introduce imaging and targeting modalities along with stimuli-response in one hybrid system, thereby incorporating multifunctionality. Fe@Au core-shell NPs possess optical signature in the visible spectrum owing to localized surface plasmon resonance (LSPR) of the Au shell, and superparamagnetic properties stemming from the Fe core. Although there exist several synthesis methods to control the size and physico-chemical properties of pNIPAm-AAc nanogels, yet, there is no comprehensive study that highlights the dependence of incorporation of one or more layers of NPs to these nanogels. In addition, effective determination of volume phase transition temperature (VPTT) of the nanogels is a challenge which complicates their uses in biological applications. Here, we have modified the swelling-collapse properties of pNIPAm-AAc nanogels, by combining with Fe@Au NPs using different solution based methods. The hydrophilic-hydrophobic transition of the nanogels above the VPTT has been confirmed to be reversible. Further, an analytical method has been developed to deduce the average VPTT which is found to be 37.3°C for the nanogels and 39.3°C for nanogel coated Fe@Au NPs. An opposite swelling –collapse behaviour is observed for the latter where the Fe@Au NPs act as bridge molecules pulling together the gelling units. Thereafter, Cyt C, a model protein drug and L-Dopa, a drug used in the clinical treatment of Parkinson’s disease were loaded separately into the nanogels and nanogel coated Fe@Au NPs, using a modified breathing-in mechanism. This gave high loading and encapsulation efficiencies (L Dopa: ~9% and 70µg/mg of nanogels, Cyt C: ~30% and 10µg/mg of nanogels respectively for both the drugs. The release kinetics of L-Dopa, monitored using UV-vis spectrophotometry was observed to be rather slow (over several hours) with highest release happening under a combination of high temperature (above VPTT) and acidic conditions. However, the release of L-Dopa from nanogel coated Fe@Au NPs was the fastest, accounting for release of almost 87% of the initially loaded drug in ~30 hours. The chemical structure of the drug, drug incorporation method, location of the drug and presence of Fe@Au NPs largely alter the drug release mechanism and the kinetics of these nanogels and Fe@Au NPs coated with nanogels.

Keywords: controlled release, nanogels, volume phase transition temperature, l-dopa

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Authors: Kanti Sapkota, Do Hyun Lee, Sung Soo Han

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Nanocomposites have been widely used in various fields such as electronics, catalysis, and in chemical, biological, biomedical and optical fields. They display broad biomedical properties like antidiabetic, anticancer, antioxidant, antimicrobial and antibacterial activities. Moreover, nanomaterials have been used for wastewater treatment. Particularly, bimetallic hybrid nanocomposites exhibit unique features as compared to their monometallic components. Hybrid nanomaterials not only afford the multifunctionality endowed by their constituents but can also show synergistic properties. In addition, these hybrid nanomaterials have noteworthy catalytic and optical properties. Notably, Au−Ag based nanoparticles can be employed in sensor and catalysis due to their characteristic composition-tunable plasmonic properties. Due to their importance and usefulness, various efforts were developed for their preparation. Generally, chemical methods have been described to synthesize such bimetallic nanocomposites. In such chemical synthesis, harmful and hazardous chemicals cause environmental contamination and increase toxicity levels. Therefore, ecologically benevolent processes for the synthesis of nanomaterials are highly desirable to diminish such environmental and safety concerns. In this regard, here we disclose a simple, cost-effective, external additive free and eco-friendly method for the synthesis of Au-Ag@AgCl nanocomposites using Nephrolepis cordifolia root extract. Au-Ag@AgCl NCs were obtained by the simultaneous reduction of cationic Ag and Au into AgCl in the presence of plant extract. The particle size of 10 to 50 nm was observed with the average diameter of 30 nm. The synthesized nanocomposite was characterized by various modern characterization techniques. For example, UV−visible spectroscopy was used to determine the optical activity of the synthesized NCs, and Fourier transform infrared (FT-IR) spectroscopy was employed to investigate the functional groups present in the biomolecules that were responsible for both reducing and capping agents during the formation of nanocomposites. Similarly, powder X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA) and energy-dispersive X-ray (EDX) spectroscopy were used to determine crystallinity, size, oxidation states, thermal stability and weight loss of the synthesized nanocomposites. As a synthetic application, the synthesized nanocomposite exhibited excellent catalytic activity for the multicomponent synthesis of biologically interesting quinoline molecules via domino annulation-aromatization reaction of aniline, arylaldehyde, and phenyl acetylene derivatives. Interestingly, the nanocatalyst was efficiently recycled for five times without substantial loss of catalytic properties.

Keywords: nanoparticles, catalysis, multicomponent, quinoline

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Authors: Peter. M. Kusen, Georg Wandrey, Christopher Probst, Dietrich Kohlheyer, Jochen Buchs, Jorg Pietruszkau

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Light as a stimulus provides the capability to develop regulation techniques for customizable gene expression. A great advantage is the extremely flexible and accurate dosing that can be performed in a non invasive and sterile manner even for high throughput technologies. Therefore, light regulation in a multiwell microbioreactor system was realized providing the opportunity to control gene expression with outstanding complexity. A light-regulated gene expression system in Saccharomyces cerevisiae was designed applying the strategy of caged compounds. These compounds are photo-labile protected and therefore biologically inactive regulator molecules which can be reactivated by irradiation with certain light conditions. The “caging” of a repressor molecule which is consumed after deprotection was essential to create a flexible expression system. Thereby, gene expression could be temporally repressed by irradiation and subsequent release of the active repressor molecule. Afterwards, the repressor molecule is consumed by the yeast cells leading to reactivation of gene expression. A yeast strain harboring a construct with the corresponding repressible promoter in combination with a fluorescent marker protein was applied in a Photo-BioLector platform which allows individual irradiation as well as online fluorescence and growth detection. This device was used to precisely control the repression duration by adjusting the amount of released repressor via different irradiation times. With the presented screening platform the regulation of complex expression procedures was achieved by combination of several repression/derepression intervals. In particular, a stepwise increase of temporally-constant expression levels was demonstrated which could be used to study concentration dependent effects on cell functions. Also linear expression rates with variable slopes could be shown representing a possible solution for challenging protein productions, whereby excessive production rates lead to misfolding or intoxication. Finally, the very flexible regulation enabled accurate control over the expression induction, although we used a repressible promoter. Summing up, the continuous online regulation of gene expression has the potential to synchronize gene expression levels to optimize metabolic flux, artificial enzyme cascades, growth rates for co cultivations and many other applications addicted to complex expression regulation. The developed light-regulated expression platform represents an innovative screening approach to find optimization potential for production processes.

Keywords: caged-compounds, gene expression regulation, optogenetics, photo-labile protecting group

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Authors: Rima Alfaraj, Abeer Alarawi, Murtadha AlTammar

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The global energy landscape heavily relies on the oil and gas industry, which faces the critical challenge of reducing its carbon footprint. To address this issue, the integration of advanced materials like aerogels has emerged as a promising solution to enhance sustainability and environmental performance within the industry. This study thoroughly examines the application of aerogel-based technologies in the oil and gas sector, focusing particularly on their role in carbon capture and storage (CCS) initiatives. Aerogels, known for their exceptional properties, such as high surface area, low density, and customizable pore structure, have garnered attention for their potential in various CCS strategies. The review delves into various fabrication techniques utilized in producing aerogel materials, including sol-gel, supercritical drying, and freeze-drying methods, to assess their suitability for specific industry applications. Beyond fabrication, the practicality of aerogel materials in critical areas such as flow assurance, enhanced oil recovery, and thermal insulation is explored. The analysis spans a wide range of applications, from potential use in pipelines and equipment to subsea installations, offering valuable insights into the real-world implementation of aerogels in the oil and gas sector. The paper also investigates the adsorption and storage capabilities of aerogel-based sorbents, showcasing their effectiveness in capturing and storing carbon dioxide (CO₂) molecules. Optimization of pore size distribution and surface chemistry is examined to enhance the affinity and selectivity of aerogels towards CO₂, thereby improving the efficiency and capacity of CCS systems. Additionally, the study explores the potential of aerogel-based membranes for separating and purifying CO₂ from oil and gas streams, emphasizing their role in the carbon capture and utilization (CCU) value chain in the industry. Emerging trends and future perspectives in integrating aerogel-based technologies within the oil and gas sector are also discussed, including the development of hybrid aerogel composites and advanced functional components to further enhance material performance and versatility. By synthesizing the latest advancements and future directions in aerogel used for CCS applications in the oil and gas industry, this review offers a comprehensive understanding of how these innovative materials can aid in transitioning towards a more sustainable and environmentally conscious energy landscape. The insights provided can assist in strategic decision-making, drive technology development, and foster collaborations among academia, industry, and policymakers to promote the widespread adoption of aerogel-based solutions in the oil and gas sector.

Keywords: CCS, porous, carbon capture, oil and gas, sustainability

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Authors: Michalina Aniola, Andrzej Katrusiak

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4,4-Bipyridine is an important compound often used in chemical practice and more recently frequently applied for designing new metal organic framework (MoFs). Here we present a systematic high-pressure study of its hydrobromide salt. 4,4-Bipyridine hydrobromide monohydrate, 44biPyHBrH₂O, at ambient-pressure is orthorhombic, space group P212121 (phase a). Its hydrostatic compression shows that it is stable to 1.32 GPa at least. However, the recrystallization above 0.55 GPa reveals a new hidden b-phase (monoclinic, P21/c). Moreover, when the 44biPyHBrH2O is heated to high temperature the chemical reactions of this compound in methanol solution can be observed. High-pressure experiments were performed using a Merrill-Bassett diamond-anvil cell (DAC), modified by mounting the anvils directly on the steel supports, and X-ray diffraction measurements were carried out on a KUMA and Excalibur diffractometer equipped with an EOS CCD detector. At elevated pressure, the crystal of 44biPyHBrH₂O exhibits several striking and unexpected features. No signs of instability of phase a were detected to 1.32 GPa, while phase b becomes stable at above 0.55 GPa, as evidenced by its recrystallizations. Phases a and b of 44biPyHBrH2O are partly isostructural: their unit-cell dimensions and the arrangement of ions and water molecules are similar. In phase b the HOH-Br- chains double the frequency of their zigzag motifs, compared to phase a, and the 44biPyH+ cations change their conformation. Like in all monosalts of 44biPy determined so far, in phase a the pyridine rings are twisted by about 30 degrees about bond C4-C4 and in phase b they assume energy-unfavorable planar conformation. Another unusual feature of 44biPyHBrH2O is that all unit-cell parameters become longer on the transition from phase a to phase b. Thus the volume drop on the transition to high-pressure phase b totally depends on the shear strain of the lattice. Higher temperature triggers chemical reactions of 44biPyHBrH2O with methanol. When the saturated methanol solution compound precipitated at 0.1 GPa and temperature of 423 K was required to dissolve all the sample, the subsequent slow recrystallization at isochoric conditions resulted in disalt 4,4-bipyridinium dibromide. For the 44biPyHBrH2O sample sealed in the DAC at 0.35 GPa, then dissolved at isochoric conditions at 473 K and recrystallized by slow controlled cooling, a reaction of N,N-dimethylation took place. It is characteristic that in both high-pressure reactions of 44biPyHBrH₂O the unsolvated disalt products were formed and that free base 44biPy and H₂O remained in the solution. The observed reactions indicate that high pressure destabilized ambient-pressure salts and favors new products. Further studies on pressure-induced reactions are carried out in order to better understand the structural preferences induced by pressure.

Keywords: conformation, high-pressure, negative area compressibility, polymorphism

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

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For chemotherapy, a drug delivery system should be able to specifically target cancer cells and deliver the therapeutic dose without affecting normal cells. Folate receptors (FR) can be considered key targets since they are commonly over-expressed in cancer cells and they are the molecular marker used in this study. Here, cyclodextrin (CD) has being studied as a vehicle for delivering the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within the CD cavity. In this study, β-CD has been modified using folic acid so as to specifically target the FR molecular marker. Thus, the system studied here for drug delivery consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 9.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 10.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 8.5 for A549 and 132.6 µM ± 12.1 and 288.1 µM ± 16.3 for BEAS-2B. These results demonstrate that MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug.

Keywords: cyclodextrins, cancer treatment, drug delivery, folate receptors, reduced folate carriers

Procedia PDF Downloads 287

Authors: Sarah K. Amer, Walaa Alaa

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Epilepsy is an important cause of mortality and morbidity, according to WHO statistics. It is characterized by the presence of frequent seizures occurring more than 24 hours apart. Carbamazepine (CBZ) is considered first-line treatment for epilepsy. However, reports have shown that CBZ oral formulations failed to achieve optimum systemic delivery, minimize side effects, and enhance patient compliance. Besides, the literature has signified the lack of therapeutically efficient CBZ transdermal formulation and the urge for its existence owing to its ease and convenient method of application and highlighted capability to attain higher bioavailability and more extended-release profiles compared to conventional oral CBZ tablets. This work aims to prepare CBZ microspheres (MS) that are embedded in a transdermal gel containing Vitamin B to be co-delivered. MS were prepared by emulsion-solvent diffusion method using Eudragit S as core forming polymer and hydroxypropyl methylcellulose (HPMC) polymer. The MS appeared to be spherical and porous in nature, offering a large surface area and high entrapment efficiency of CBZ. The transdermal gel was prepared by solvent-evaporation technique using HPMC that, offered high entrapment efficiency and Eudragit S that provided an extended-release profile. Polyethylene glycol, Span 80 and Pyridoxine were also added. Data indicated that combinations of CBZ with pyridoxine can reduce epileptic seizures without affecting motor coordination. Extended-release profiles were evident for this system. The patches were furthermore tested for thickness, moisture content, folding endurance, spreadability and viscosity measurements. This novel pharmaceutical formulation would be of great influence on seizure control, offering better therapeutic effects.

Keywords: epilepsy, carbamazepine, pyridoxine, transdermal

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Authors: Jafar Akbari

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Quinolines are very important compounds partially because of their pharmacological properties which include wide applications in medicinal chemistry. notable among them are antimalarial drugs, anti-inflammatory agents, antiasthamatic, antibacterial, antihypertensive, and tyrosine kinase inhibiting agents. Despite quinoline usage in pharmaceutical and other industries, comparatively few methods for their preparation have been reported.The Friedlander annulation is one of the simplest and most straightforward methods for the synthesis of poly substituted quinolines. Although, modified methods employing lewis or br¢nsted acids have been reported for the synthesis of quinolines, the development of water stable acidic catalyst for quinoline synthesis is quite desirable. One of the most remarkable features of ionic liquids is that the yields can be optimized by changing the anions or the cations. Recently, sulfonic acid functionalized ionic liquids were used as solvent-catalyst for several organic reactions. We herein report the one pot domino approach for the synthesis of quinoline derivatives in Friedlander manner using TSIL as a catalyst. These ILs are miscible in water, and their homogeneous system is readily separated from the reaction product, combining advantages of both homogeneous and heterogeneous catalysis. In this reaction, the catalyst plays a dual role; it ensures an effective condensation and cyclization of 2-aminoaryl ketone with second carbonyl group and it also promotes the aromatization to the final product. Various types of quinolines from 2-aminoaryl ketones and β-ketoesters/ketones were prepared in 85-98% yields using the catalytic system of SO3-H functionalized ionic liquid/H2O. More importantly, the catalyst could be easily recycled for five times without loss of much activity.

Keywords: antimalarial drugs, green chemistry, ionic liquid, quinolines

Procedia PDF Downloads 188

Authors: Anita K. Kovacs, Peter Hegyes, Zsolt Bozso, Gabor Toth

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Fluorination has been used extensively by the pharmaceutical industry as a strategy to improve the pharmacokinetics of drugs due to its effectiveness in increasing the potency of antimicrobial peptides (AMPs). Multiple-fluorinated indole-ring-containing tryptophan derivatives have the potential of having better antimicrobial activity than the widely used mono-fluorinated indole-ring containing tryptophan derivatives, but they are not available commercially. Therefore, our goal is to synthesize multiple-fluorinated indole-ring containing tryptophan derivatives to incorporate them into AMPs to enhance their antimicrobial activity. During our work, we are trying several methods (classical organic synthesis, enzymic synthesis, and solid phase peptide synthesis) for the synthesis of the said compounds, with mixed results. With classical organic synthesis (four different routes), we did not get the desired results. The reaction of serin with substituted indole in the presence of acetic anhydride led to racemic tryptophane; with the reaction of protected serin with indole in the presence of nickel complex was unsuccessful; the reaction of serin containing protected dipeptide with disuccinimidyl carbonate we achieved a tryptophane containing dipeptide, its chiral purity is being examined; the reaction of alcohol with substituted indole in the presence of copper complex was successful, but it was only a test reaction, we could not reproduce the same result with serine. The undergoing tryptophan-synthase method has shown some potential, but our work has not been finished yet. The successful synthesis of the desired multiple-fluorinated indole-ring-containing tryptophan will be followed by solid phase peptide synthesis in order to incorporate it into AMPs to enhance their antimicrobial activity. The successful completion of these phases will mean the possibility of manufacturing new, effective AMPs.

Keywords: halogenation, fluorination, tryptophan, enhancement of antimicrobial activity

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Authors: Gajanan M. Sonwane

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Nowadays, the entire pharmaceutical industry is facing the challenge of increasing efficiency and innovation. The major hurdles are the growing cost of research and development and a concurrent stagnating number of new chemical entities (NCEs). Hence, the challenge is to select the most druggable targets and to search the equivalent drug-like compounds, which also possess specific pharmacokinetic and toxicological properties that allow them to be developed as drugs. The present research work includes the studies of developing new anticancer heterocycles by using molecular modeling techniques. The heterocycles synthesized through such methodology are much effective as various physicochemical parameters have been already studied and the structure has been optimized for its best fit in the receptor. Hence, on the basis of the literature survey and considering the need to develop newer anticancer agents, new phenazinamine derivatives were designed by subjecting the nucleus to molecular modeling, viz., GQSAR analysis and docking studies. Simultaneously, these designed derivatives were subjected to in silico prediction of biological activity through PASS studies and then in silico toxicity risk assessment studies. In PASS studies, it was found that all the derivatives exhibited a good spectrum of biological activities confirming its anticancer potential. The toxicity risk assessment studies revealed that all the derivatives obey Lipinski’s rule. Amongst these series, compounds 4c, 5b and 6c were found to possess logP and drug-likeness values comparable with the standard Imatinib (used for anticancer activity studies) and also with the standard drug methotrexate (used for antimitotic activity studies). One of the most notable mutations is the threonine to isoleucine mutation at codon 315 (T315I), which is known to be resistant to all currently available TKI. Enzyme assay planned for confirmation of target selective activity.

Keywords: drug design, tyrosine kinases, anticancer, Phenazinamine

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Authors: Nicola G. G. Cecca

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In Italian IPSSEOAs, high schools that give a vocational education to students that will work in the field of Enogastronomy and Hotel Management, the course of Food Science allows the students to start and see food as a mixture of substances that they will transform during their profession. These substances are characterized not only by a chemical composition but also by a molecular structure that makes them nutritionally active. But the increasing number of new products proposed by Food Industry, the modern techniques of production and transformation, the innovative preparations required by customers have made many information reported in the most wide spread Food Science textbooks not up-to-date or too poor for the people who will work in catering sector. Often Authors offer information aged to Bohr’s Atomic Model and to the ‘Octet Rule’ proposed by G.N. Lewis to describe the Chemical Bond, without giving any reference to new as Orbital Atomic Model and Molecular Orbital Theory that, in the meantime, start to be old themselves. Furthermore, this antiquated information precludes an easy understanding of a wide range of properties of nutritive substances and many reactions in which the food constituents are involved. In this paper, our attention is pointed out to use GEOMAG™ to represent the dynamics with which the chemical bond is formed during the synthesis of the molecules. GEOMAG™ is a toy, produced by the Swiss Company Geomagword S.A., pointed to stimulate in children, aged between 6-10 years, their fantasy and their handling ability and constituted by metallic spheres and metallic magnetic bars coated by coloured plastic materials. The simulation carried out with GEOMAG™ is based on the similitude existing between the Coulomb’s force and the magnetic attraction’s force and in particular between the formulae with which they are calculated. The electrostatic force (F in Newton) that allows the formation of the chemical bond can be calculated by mean Fc = kc q1 q2/d2 where: q1 e q2 are the charge of particles [in Coulomb], d is the distance between the particles [in meters] and kc is the Coulomb’s constant. It is surprising to observe that the attraction’s force (Fm) acting between the magnetic extremities of GEOMAG™ used to simulate the chemical bond can be calculated in the same way by using the formula Fm = km m1 m2/d2 where: m1 e m2 represent the strength of the poles [A•m], d is the distance between the particles [m], km = μ/4π in which μ is the magnetic permeability of medium [N•A-2]. The magnetic attraction can be tested by students by trying to keep the magnetic elements of GEOMAG™ separate by hands or trying to measure by mean an appropriate dynamometric system. Furthermore, by using a dynamometric system to measure the magnetic attraction between the GEOMAG™ elements is possible draw a graphic F=f(d) to verify that the curve obtained during the simulation is very similar to that one hypnotized, around the 1920’s by Linus Pauling to describe the formation of H2+ in according with Molecular Orbital Theory.

Keywords: chemical bond, molecular orbital theory, magnetic attraction force, GEOMAG™

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Authors: Jungkyun Im

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Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective for relieving pain and reducing inflammation. They are nonselective inhibitors of two isoforms of COX, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and thereby inhibiting the production of hormone-like lipid compounds such as, prostaglandins and thromboxanes which cause inflammation, pain, fever, platelet aggregation, etc. In addition, recently there are many research articles reporting the neuroprotective effect of NSAIDs in neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). However, the clinical use of NSAIDs in these diseases is limited by low brain distribution. Therefore, in order to assist the in-depth investigation on the pharmaceutical mechanism of flurbiprofen in neuroprotection and to make flurbiprofen a more potent drug to prevent or alleviate neurodegenerative diseases, delivery of flurbiprofen to brain should be effective and sufficient amount of flurbiprofen must penetrate the BBB thus gaining access into the patient’s brain. We have recently developed several types of guanidine-rich molecular carriers with high molecular weights and good water solubility that readily cross the blood-brain barrier (BBB) and display efficient distributions in the mouse brain. The G8 (having eight guanidine groups) molecular carrier based on D-sorbitol was found to be very effective in delivering anticancer drugs to a mouse brain. In the present study, employing the same molecular carrier, we prepared the flurbiprofen conjugate and studied its BBB permeation by mouse tissue distribution study. Flurbiprofen was attached to a molecular carrier with a fluorescein probe and multiple terminal guanidiniums. The conjugate was found to internalize into live cells and readily cross the BBB to enter the mouse brain. Our novel synthetic flurbiprofen conjugate will hopefully delivery NSAIDs into brain, and is therefore applicable to the neurodegenerative diseases treatment or prevention.

Keywords: flurbiprofen, drug delivery, molecular carrier, organic synthesis

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Authors: Muslihatus Syarifah

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Introduction: Rosella flower petals can be used as an antibacterial because it contains alkaloids, flavonoids, phenolics, and terpenoids) for the . Bacteria activity is S. aureus can cause skin infections and pengobatanya most appropriate use of topical preparations. Ointment is a topical preparation comprising the active substance and ointment base. Not all the base matches the active substances or any type of disease. In this study using flavonoid active substances contained in rosella flower petals (Hibiscus sabdariffa) to be made ointment by testing a variety of different bases in order to obtain a suitable basis for the formulation of ointment extract rosella flower petals. Methods: Experimental research with research methods Post test control group design using the ointment is hydrocarbon sample, absorption, leached water and dissolved water. Then tested for bacteria S. aureus with different concentrations of 1%, 2%, 4%, 8%, 16, 32%. Data were analyzed using One Way ANOVA followed by Post Hoc test. Results: Ointment with a hydrocarbon base, absorption, leached water and dissolved water having no change in physical properties during storage. Base affect the physical properties of an ointment that adhesion, dispersive power and pH. The physical properties of the ointment with different concentrations produce different physical properties including adhesion, dispersive power and pH. The higher the concentration the higher dispersive power, but the smaller the adhesion and pH. Conclusion: Differences bases, storage time, the concentration of the extract can affect the physical properties of the ointment. Concentration of extract in the ointment extract rosella flower petals is 32%.

Keywords: rosella, physical properties, ointments, antibacterial

Procedia PDF Downloads 352

Authors: Deepali Rastogi

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Natural dyes are considered to be eco-friendly as they cause no pollution and are safe to use. With the growing interest in natural dyes, new sources of natural dyes are being explored. Coconut (Cocos nucifera) is native to tropical eastern region. It is abundantly available in Asia, Africa and South America. While coconut has tremendous commercial value in food, oil, pharmaceutical and cosmetic industry, the most important use of coconut husk has been as coir which is used for making mats, ropes, etc. In the present study an attempt has been made to extract dye from the coconut husk and study its application on wool and silk. Dye was extracted from coconut husk in an aqueous medium at three different pH. The coconut husk fibres were boiled in water at different pH of 4, 7 and 9 for one hour. On visual inspection of the extracted dye solution, maximum colour was found to be extracted at pH 9. The solution was obtained in neutral medium whereas, no dye was extracted in acidic medium. Therefore, alkaline medium at pH 9 was selected for the extraction of dye from coconut husk. The extracted dye was applied on wool and silk at three different pH, viz., 4, 7 and 9. The effect of pre- and post- mordanting with alum and ferrous sulphate on the colour value of coconut husk dye was also studied. The L*a*b*/L*c*h* values were measured to see the effect of the mordants on the colour values of all the dyed and mordanted samples. Bright golden brown to dark brown colours were obtained at pH 4 on both wool and silk. The colour yield was not very good at pH 7 and 9. Mordanting with alum resulted in darker and brighter shades of brown, whereas mordanting with ferrous sulphate resulted in darker and duller shades. All the samples were tested for colourfastness to light, rubbing, washing and perspiration. Both wool and silk dyed with dye extracted from coconut husk exhibited good to excellent wash, rub and perspiration fastness. Fastness to light was moderate to good.

Keywords: coconut husk, wool, silk, natural dye, mordants

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Authors: Safaa S. Hassan, Mohammed H. Elbakry, Safwat A. Mangoura, Zainab M. Omar

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Background: Liver fibrosis is the main reason for increased mortality in chronic liver disease. It has no standard treatment. Antioxidants from a variety of sources are capable of slowing or preventing oxidation of other molecules. Aim: to evaluate the hepatoprotective effect of vit. C, vit. E and gallic acid in comparison to silymarin in the rat model of carbon tetrachloride induced liver fibrosis and their possible mechanisms of action. Material& Methods: A total number of 60 adult male albino rats 160-200gm were divided into six equal groups; received subcutaneous (s.c) injection for 8 weeks. Group I: as control. Group II: received 1.5 mL/kg of CCL4 .Group III: CCL4 and co- treatment with silymarin 100mg/kg p.o. daily. Group IV: CCL4 and co-treatment with vit. C 50mg/kg p.o. daily. Group V: CCL4 and co-treatment with vit. E 200mg/kg. p.o. Group VI: CCL4 and co-treatment with Gallic acid 100mg/kg. p.o. daily. Liver was processed for histological and immunohistochemical examination. Levels of AST, ALT, ALP, reduced GSH, MDA, SOD and hydroxyproline concentration were measured and evaluated statistically. Results: Light and electron microscopic examination of liver of group II exhibited foci of altered cells with dense nuclei and vacuolated, granular cytoplasm, mononuclear cell infiltration in portal areas, profuse collagen fiber deposits were found around portal tract, more intense staining α-SMA-positive cells occupied most of the liver fibrosis tissue, electron lucent areas in the cytoplasm of the hepatocytes, margination of nuclear chromatin. Treatment by any of the antioxidants variably reduced the hepatic structural changes induced by CCL4. Biochemical analysis showed that carbon tetrachloride significantly increased the levels of serum AST, ALT, ALP, hepatic malondialdehyde and hydroxyproline content. Moreover, it decreased the activities of superoxide dismutase and glutathione. Treatment with silymarin, gallic acid, vit. C and vit. E decreased significantly the AST, ALT, and ALP levels in plasma, MDA and hydroxyproline and increased the activities of SOD and glutathione in liver tissue. The effect of administration of CCl4 was improved with the used antioxidants in variable degrees. The most efficient antioxidant was silymarin followed by gallic acid and vit. C then vit. E. It is possibly due to their antioxidant effect, free radical scavenging properties and the reduction of oxidant dependent activation and proliferation of HSCs. Conclusion: So these antioxidants can be a promising drugs candidate for ameliorating liver fibrosis better than the use of the drugs and their side effects.

Keywords: antioxidant, ccl4, gallic acid, liver fibrosis

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Authors: A. Hamza, H. Kathyayini, N. Nagaraju

Abstract:

Aluminophosphates, both amorphous and crystalline materials find applications as adsorbents, ceramics, and pigments and as catalysts/catalyst supports in organic fine chemical synthesis. Most of the applications are varied depending on the type of metal incorporated, particle size, surface area, porosity and morphology of aluminophosphate. The porous and surface properties of these materials are normally fine-tuned by adopting various preparation methodologies. Numerous crystalline microporous and mesoporous aluminophosphates and metal-aluminophosphates have been reported in literature, in which the synthesis has been carried out by using structure directing organic molecules/surfactants. In present work, amorphous aluminophosphate (AlP) and metal-aluminophosphates MAlP (M = Cu, Zn, Cr, Fe, Ce and Zr) and their mixed forms M-1M2AlP are prepared under a typical precipitation condition, i.e. at low temperature in order to keep the Von-Weirmann relative super saturation of the precipitating medium and obtain small size precipitate particles. These materials are prepared without using any surfactants. All materials are thoroughly characterised for surface and bulk properties by N2 adsorption-desorption technique, XRD, FT-IR, TG and SEM. The materials are also analysed for the amount and the strength of their surface acid sites, by NH3-TPD and CO2-TPD techniques respectively. All the materials prepared in the work are investigated for their catalytic activity in following applications in the synthesis of industrially important Jasminaldehyde via, aldol condensation of n-heptanal and benzaldehyde, in the synthesis of biologically important chalcones by Claisen-shmidth condensation of benzaldehyde and substituted chalcones. The effect of the amount of the catalysts, duration of the reaction, temperature of the reaction, molar ratio of the reactants has been studied. The porosity of pure aluminophosphate is found to be changed significantly by the incorporation of transition metals during preparation of aluminophosphate. The pore size increased from microporous to mesoporous and finally to macroporous by following order of metals Cu = Zn < Cr < Ce < Fe = Zr. The change in surface area and porosity of double metal-aluminophosphates depended on the concentration of both the metals. The acidity of aluminophosphate is either increased or decreased which depended on the type and valence of metals loaded. A good number of basic sites are created in metal-aluminophosphates irrespective of the metals used. A maximum catalytic activity for synthesis of both jasminaldehyde and chalcone is obtained by FeAlP as catalysts; these materials are characterized by decreased strength and concentration of acidic sites with optimum level basic sites.

Keywords: amorphous metal-aluminophosphates, surface properties, acidic-basic properties, Aldol, Claisen-Shmidth condensation, jasminaldehyde, chalcone

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