Search results for: Molecular modeling of 17-picolyl and 17-picolinylidene androstane derivatives with anticancer activity

Authors: Alma Ramić, Mirjana Skočibušić, Renata Odžak, Tomica Hrenar, Ines Primožič

Abstract:

In an attempt to identify a new class of antimicrobial agents, the antimicrobial potential of Cinchona alkaloid derivatives was evaluated. The bark of the Cinchona trees is the source of a variety of alkaloids, among which the best known are quinine, quinidine, cinchonine and cinchonidine. They are very useful as organocatalysts in stereoselective synthesis. On the other hand, quinine is traditionally used in the treatment of malaria. Furthermore, Cinchona alkaloids possess various analgesic, anti-inflammatory and anti–arrhythmic properties as well. In this work we present the synthesis of twenty quaternary derivatives of pseudo−enantiomeric Cinchona alkaloid derivatives to evaluate their antibacterial activity. Quaternization of quinuclidine moiety was carried out with groups diverse in their size. The structures of compounds were systematically modified to obtain drug-like properties with proper physical and chemical properties and avoiding toxophore. All compounds were prepared in good yields and were characterized by standard analytical spectroscopy methods (1D and 2D NMR, IR, MS). The antibacterial activities of all compounds were evaluated against series of recent clinical isolates of antibiotic susceptible Gram-positive and resistant Gram-negative pathogens by determining their zone of inhibition and minimum inhibitory concentrations. All compounds showed good to strong broad-spectrum activity, equivalent or better in comparison with standard antibiotics used. Furthermore, seven compounds exhibited significant antibacterial efficiency against Gram-negative isolates. To visualize the results, principal component analysis was used as an additional classification tool. Cytotoxicity of compounds with different cell lines in human cell culture was determined. Based on these results, substituted quaternary Cinchona scaffold can be considered as promising new class of antimicrobials and further investigations should be performed. Supported by Croatian Science Foundation, Project No 3775 ADESIRE.

Keywords: antibacterial efficiency, cinchona alkaloids, cytotoxicity, pseudo‐enantiomers

Procedia PDF Downloads 139

Authors: Sankarprasad Bhuniya, Sukhendu Maiti, Eun-Joong Kim, Hyunseung Lee, Jonathan L. Sessler, Kwan Soo Hong, Jong Seung Kim

Abstract:

A new theranostic strategy is described. It is based on the use of an “all in one” prodrug, namely the biotinylated piperazine-rhodol conjugate 4a. This conjugate, which incorporates the anticancer drug SN-38, undergoes self-immolative cleavage when exposed to biological thiols. This leads to the tumor-targeted release of the active SN-38 payload along with fluorophore 1a. This release is made selective as the result of the biotin functionality. Fluorophore 1a is 32-fold more fluorescent than prodrug 4a. It permits the delivery and release of the SN-38 payload to be monitored easily in vitro and in vivo, as inferred from cell studies and ex vivo analyses of mice xenografts derived HeLa cells, respectively. Prodrug 4a also displays anticancer activity in the HeLa cell murine xenograft tumor model. On the basis of these findings we suggest that the present strategy, which combines within a single agent the key functions of targeting, release, imaging, and treatment, may have a role to play in cancer diagnosis and therapy.

Keywords: theranostic, prodrug, cancer therapy, fluorescence

Procedia PDF Downloads 520

Authors: Marwa M. Abu-Serie, Marwa M. Eltarahony

Abstract:

The search for reliable, effective, and safe nanoparticles (NPs) as a treatment for cancer is a pressing priority. In this study, Cu-NPs were fabricated by Streptomyces cyaneofuscatus through simultaneous bioreduction strategy of copper nitrate salt. The as-prepared Cu-NPs subjected to structural analysis; energy-dispersive X-ray spectroscopy, elemental mapping, X-ray diffraction, transmission electron microscopy, and ζ-potential. These biological synthesized Cu-NPs were mixed with disulfiram (DS), forming a nanocomplex of Cu-DS with a size of ~135 nm. The prepared nanocomplex (nanoCu-DS) exhibited higher anticancer activity than that of free complex of DS-Cu, Cu-NPs, and DS alone. This was illustrated by the lowest IC50 of nanoCu-DS (< 4 µM) against human breast and liver cancer cell lines comparing with DS-Cu, Cu-NPs, and DS (~8, 22.98-33.51 and 11.95-14.86, respectively). Moreover, flow cytometric analysis confirmed that higher apoptosis percentage range of nanoCu-DS-treated in MDA-MB 231, MCF-7, Huh-7, and HepG-2 cells (51.24-65.28%) than free complex of Cu-DS ( < 4.5%). Regarding inhibition potency of liver and breast cancer cell migration, no significant difference was recorded between free and nanocomplex. Furthermore, nanoCu-DS suppressed gene expression of β-catenine, Akt, and NF-κB and upregulated p53 expression (> 3, >15, > 5 and ≥ 3 folds, respectively) more efficiently than free complex (all ~ 1 fold) in MDA-MB 231 and Huh-7 cells. Our finding proved this prepared nano complex has a powerful anticancer activity relative to free complex, thereby offering a promising cancer treatment.

Keywords: biologically prepared Cu-NPs, breast cancer cell lines, liver cancer cell lines, nanoCu- disulfiram

Procedia PDF Downloads 170

Authors: Ram V. Mohan, John Rivas-Murillo, Ahmed Mohamed, Wayne D. Hodo

Abstract:

Cementitious materials, an excellent example of highly complex, heterogeneous material systems, are cement-based systems that include cement paste, mortar, and concrete that are heavily used in civil infrastructure; though commonly used are one of the most complex in terms of the material morphology and structure than most materials, for example, crystalline metals. Processes and features occurring at the nanometer sized morphological structures affect the performance, deformation/failure behavior at larger length scales. In addition, cementitious materials undergo chemical and morphological changes gaining strength during the transient hydration process. Hydration in cement is a very complex process creating complex microstructures and the associated molecular structures that vary with hydration. A fundamental understanding can be gained through multi-scale level modeling for the behavior and properties of cementitious materials starting from the material chemistry level atomistic scale to further explore their role and the manifested effects at larger length and engineering scales. This predictive modeling enables the understanding, and studying the influence of material chemistry level changes and nanomaterial additives on the expected resultant material characteristics and deformation behavior. Atomistic-molecular dynamic level modeling is required to couple material science to engineering mechanics. Starting at the molecular level a comprehensive description of the material’s chemistry is required to understand the fundamental properties that govern behavior occurring across each relevant length scale. Material chemistry level models and molecular dynamics modeling and simulations are employed in our work to describe the molecular-level chemistry features of calcium-silicate-hydrate (CSH), one of the key hydrated constituents of cement paste, their associated deformation and failure. The molecular level atomic structure for CSH can be represented by Jennite mineral structure. Jennite has been widely accepted by researchers and is typically used to represent the molecular structure of the CSH gel formed during the hydration of cement clinkers. This paper will focus on our recent work on the shear and compressive deformation and failure behavior of CSH represented by Jennite mineral structure that has been widely accepted by researchers and is typically used to represent the molecular structure of CSH formed during the hydration of cement clinkers. The deformation and failure behavior under shear and compression loading deformation in traditional hydrated CSH; effect of material chemistry changes on the predicted stress-strain behavior, transition from linear to non-linear behavior and identify the on-set of failure based on material chemistry structures of CSH Jennite and changes in its chemistry structure will be discussed.

Keywords: cementitious materials, deformation, failure, material chemistry modeling

Procedia PDF Downloads 270

Authors: Mala Nath, Nagamani Kompelli, Partha Roy, Snehasish Das

Abstract:

Two new metal-based anticancer chemotherapeutic agents, [(Ph2Sn)2(HGuO)2(phen)Cl2] 1 and [(Ph3Sn)(HGuO)(phen)]- Cl.CH3OH.H2O 2, were designed, prepared and characterized by analytical and spectral (IR, ESI-Mass, 1H, 13C and 119Sn NMR) techniques. The proposed geometry of Sn(IV) in 1 and 2 is distorted octahedral and distorted trigonal-bipyramidal, respectively. Both 1 and 2 exhibit potential cytotoxicity in vitro against MCF-7, HepG-2 and DU-145 cell lines. The intrinsic binding constant (Kb) values of 1 (2.33 × 105 M-1) and 2 (2.46 × 105 M-1) evaluated from UV-Visible absorption studies suggest non-classical electrostatic mode of interaction via phosphate backbone of DNA double helix. The Stern-Volmer quenching constant (Ksv) of 1 (9.74 × 105 M-1) and 2 (2.9 × 106 M-1) determined by fluorescence studies suggests the groove binding and intercalation mode for 1 and 2, respectively. Effective cleavage of pBR322 DNA is induced by 1. Their interaction with DNA of cancer cells may account for potency.

Keywords: anticancer agents, DNA binding studies, NMR spectroscopy, organotin

Procedia PDF Downloads 239

Authors: Jae Young Jang, Jong Hoon Ahn, Jae-Woong Lim, So Young Kang, Mi Kyeong Lee

Abstract:

Rhus verniciflua is commonly known as a lacquer tree in Korea. Stem barks of R. verniciflua have been used as an immunostimulator in traditional medicine. It contains phenolic compounds and is known for diverse biological activities such as antioxidant and antimicrobial activity. However, it also causes allergic dermatitis due to urushiols derivatives. For the development of active natural resources with less toxicity, the content of phenolic compounds and urushiols of different parts of R. verniciflua such as stem barks, lignum and leaves were quantitated by colorimetric assay and HPLC analysis. The urushiols content were the highest in stem barks, and followed by leaves. The lignum contained trace amount of urushiols. The phenolic contents, however, were the most abundant in lignum, and followed by leaves and stem barks. These results clear showed that the content of urushiols and phenolic differs depending on the parts of R. verniciflua. Antimicrobial activity of different parts of R. verniciflua against fish pathogenic bacteria was also investigated using Edwardsiella tarda. Lignum of R. verniciflua was the most effective in antimicrobial activity against E. tarda and phenolic constituents are suggested to be active constituents for activity. Taken together, phenolic compounds are responsible for antimicrobial activity of R. verniciflua. The lignum of R. verniciflua contains high content of phenolic compounds with less urushiols, which suggests efficient antimicrobial activity with less toxicity. Therefore, lignum of R. verniciflua are suggested as good sources for antimicrobial activity against fish bacterial diseases.

Keywords: different parts, phenolic compounds, Rhus verniciflua, urushiols

Procedia PDF Downloads 299

Authors: Dalvir Kataria, Khushminder Kaur Chahal, Amit Kumar

Abstract:

The carrot seed essential oil was obtained by hydrodistillation. Hexane, dichloromethane, and methanol solvents were used for extraction of carrot seed by Soxhlet extraction methods. The major and minor compounds identified in carrot seed essential oil were carotol (52.73), daucol (5.10), daucene (5.68), (E)-β-farnesene (5.40), β-cubebene (3.19), longifolenaldehyde (3.23), β-elimene (3.23), (E)-caryophyllene (1.22), β-bisabolene (2.95) etc. The chemical composition of hexane, dichloromethane, and methanol extracts was different. Carotol was the common compound present. Major compounds isolated were from the carrot seed essential oil by column chromatography. Chemical transformations of carotol (2) with mercuric acetate/sodium borohydride, dry hydrochloric acid gas, acetonitrile/sulfuric acid, selenium dioxide/t-butyl hydrogen peroxide, N-bromosuccinimide, hydrogen iodide, and phenol were carried out. The derivatives of carotol were designed to explore the significance of some structural modifications in relation to antioxidant activities. The structures of major compounds and derivatives were confirmed on the basis of FT-IR, 1HNMR and 13CNMR spectroscopy. Antioxidant activity of carrot seed essential oil, various extracts and isolated compounds were tested by in vitro models involving 2, 2-diphenyl-1-picrylhydrazyl (DPPH•), hydroxyl (OH•), nitric oxide (NO•), superoxide radical scavenging methods and ferric reducing antioxidant power assay (FRAP). Chemical transformations of major isolated compound carotol were carried out, and antioxidant activity of all compounds was undertaken. The major sesquiterpenoidcarotol isolated from carrot seed essential oil showed the highest antioxidant activity in all the methods. The methanol extract showed higher antioxidant potential as compared to carrot seed essential oil, hexane, and dichloromethane extracts.

Keywords: antioxidant, carotol, carrot, DPPH

Procedia PDF Downloads 119

Authors: Jungkyun Im

Abstract:

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

Procedia PDF Downloads 218

Authors: Jing Zhao, Yongqing Bai, Qiaofang Shi, Huaihao Zhang

Abstract:

Advances in software technology enable computational chemistry to be commonly applied in various research fields, especially in pedagogy. Thus, in order to expand and improve experimental instructions of computational chemistry for undergraduates, we designed an introductory experiment—research on acrylamide molecular structure and physicochemical properties. Initially, students construct molecular models of acrylamide and polyacrylamide in Gaussian and Materials Studio software respectively. Then, the infrared spectral data, atomic charge and molecular orbitals of acrylamide as well as solvation effect of polyacrylamide are calculated to predict their physicochemical performance. At last, rheological experiments are used to validate these predictions. Through the combination of molecular simulation (performed on Gaussian, Materials Studio) with experimental verification (rheology experiment), learners have deeply comprehended the chemical nature of acrylamide and polyacrylamide, achieving good learning outcomes.

Keywords: upper-division undergraduate, computer-based learning, laboratory instruction, molecular modeling

Procedia PDF Downloads 120

Authors: Edson Vengesai

Abstract:

Derivative products have become essential instruments in portfolio diversification, price discovery, and, most importantly, risk hedging. Derivatives are complex instruments; their valuation, volatility implications, and real impact on the underlying assets' behaviour are not well understood. Little is documented empirically, with conflicting conclusions on how these instruments affect firm risk exposures. Given the growing interest in using derivatives in risk management and portfolio engineering, this study examines the practical impact of derivative usage on the underlying stock price exposure and systematic risk. The paper uses data from South African listed firms. The study employs GARCH models to understand the effect of derivative uses on conditional stock volatility. The GMM models are used to estimate the effect of derivatives use on stocks' systematic risk as measured by Beta and on the total risk of stocks as measured by the standard deviation of returns. The results provide evidence on whether derivatives use is instrumental in reducing stock returns' systematic and total risk. The results are subjected to numerous controls for robustness, including financial leverage, firm size, growth opportunities, and macroeconomic effects.

Keywords: derivatives use, hedging, volatility, stock price exposure

Procedia PDF Downloads 90

Authors: Kevin A. Droguett, Edwin G. Pérez, Denis Fuentealba, Margarita E. Aliaga, Angélica M. Fierro

Abstract:

Supramolecular chemistry is a field of growing interest. Moreover, studying the formation of host-guest complexes between macrocycles and dyes is highly attractive due to their potential applications. Examples of the above are drug delivery, catalytic process, and sensing, among others. There are different dyes of interest in the literature; one example is the quinolinone derivatives. Those molecules have good optical properties and chemical and thermal stability, making them suitable for developing fluorescent probes. Secondly, several macrocycles can be seen in the literature. One example is the cucurbiturils. This water-soluble macromolecule family has a hydrophobic cavity and two identical carbonyl portals. Additionally, the thermodynamic analysis of those supramolecular systems could help understand the affinity between the host and guest, their interaction, and the main stabilization energy of the complex. In this work, two 7-(diethylamino) quinoline-2 (1H)-one derivative (QD1-2) and their interaction with cucurbit[7]uril (CB[7]) were studied from an experimental and in-silico point of view. For the experimental section, the complexes showed a 1:1 stoichiometry by HRMS-ESI and isothermal titration calorimetry (ITC). The inclusion of the derivatives on the macrocycle lends to an upward shift in the fluorescence intensity, and the pKa value of QD1-2 exhibits almost no variation after the formation of the complex. The thermodynamics of the inclusion complexes was investigated using ITC; the results demonstrate a non-classical hydrophobic effect with a minimum contribution from the entropy term and a constant binding on the order of 106 for both ligands. Additionally, dynamic molecular studies were carried out during 300 ns in an explicit solvent at NTP conditions. Our finding shows that the complex remains stable during the simulation (RMSD ~1 Å), and hydrogen bonds contribute to the stabilization of the systems. Finally, thermodynamic parameters from MMPBSA calculations were obtained to generate new computational insights to compare with experimental results.

Keywords: host-guest complexes, molecular dynamics, quinolin-2(1H)-one derivatives dyes, thermodynamics

Procedia PDF Downloads 69

Authors: Srisopa Ruangnoo, Arunporn Itharat

Abstract:

The ethanolic and aqueous extracts of Parkia javanica Merr. germinating seeds and Parkia speciosa Hassk. seeds were evaluated for cytotoxic activity against three different types of human cancer cell lines including colon cancer (LS174T), breast cancer (MCF-7) and prostate cancer (PC3) using sulforhodamine B (SRB) assay. The fresh plant parts were divided into 2 parts. The first part was extracted by maceration with 95% ethanol for 3 days and then filtered, and the filtrates were evaporated by rotary evaporator. The other part was squeezed and filtered. Then the filtrates were dried by freeze dryer. The screening found that the aqueous extract of P. javanica Merr. germinating seeds exhibited more than 70% inhibition (at concentration 50 µg/ml) against all types of human cancer cells. The aqueous extract of P. javanica Merr. germinating seeds showed the highest cytotoxic activity against MCF-7 with the IC50 value as 5.63 µg/ml. The aqueous extract of P. javanica Merr. germinating seeds also showed high cytotoxic activity against PC3 and LS174T with the IC50 values as 10.79 and 11.40 µg/ml, respectively. In conclusion, P. javanica Merr. germinating seed is a natural source of anticancer activity and further research to isolate active compounds from this plant should be undertaken.

Keywords: cytotoxic activity, Parkia javanica Merr., Parkia speciosa Hassk., human cancer cell lines

Procedia PDF Downloads 396

Authors: Anas Al-Ali, Mohammed Suleiman, Ayman Hussein

Abstract:

Sulfur is an important element has many practical applications in present as nanoparticles. Nanosize sulfur particles also have many important applications like in pharmaceuticals, medicine, synthesis of nanocomposites for lithium batteries, modification of carbon nanotubes. Different methods were used for nano-sized particle synthesis; among those, chemical precipitation, electrochemical method, micro-emulsion technique, composing of oil, surfactant, co-surfactant, aqueous phases with the specific compositions and ultrasonic treatment of sulfur-cystine solution. In this work, sulfur nanoparticles (S NPs) were prepared by a quick precipitation method with and without using a surfactant to stabilize the formed S NPs. The synthesized S NPs were characterized by XRD, SEM, and TEM in order to confirm their sizes and structures. Application of nanotechnology is suggested for diagnosis and treatment of cancer. The anticancer activity of the prepared S NPs has been tested on various types of cancer cell clones including leukemia, kidney and colon cancers.

Keywords: sulfur nanoparticles (S-NPs), TEM, SEM, anti cancer activity, XRD

Procedia PDF Downloads 501

Authors: Arianna Zhu, Thomas Bakupog

Abstract:

Taxol (generic name paclitaxel) is an antineoplastic drug used to treat breast, lung, and ovarian cancer. It performs exceptionally well against a wide variety of tumors, including B16 melanoma, L1210 and P388 leukemias, MX-1 mammary tumors, and CX-1 colon tumor xenografts. However, despite taxol’s efficacy in antitumor activity, its aqueous solubility is extremely poor, decreasing its bioavailability and making it difficult for the body to absorb. The objective of this study is to improve the solubility of taxol, thus increasing the bioavailability of the drug in preventing cancer. By modifying the structure of taxol, four novel taxol derivatives were created with improved solubilities. Two of the derivatives were given an additional hydrogen donor and acceptor and thus showed a pronounced positive change in solubility. The results of this work solve the issue of taxol’s inadequate solubility and show potential in increasing the absorption of the drug.

Keywords: Taxol, Solubility, improving bioavailability, logP

Procedia PDF Downloads 48

Authors: Aparna Viswanath

Abstract:

Electricity spot prices are highly volatile under optimal generation capacity scenarios due to factors such as non-storability of electricity, peak demand at certain periods, generator outages, fuel uncertainty for renewable energy generators, huge investments and time needed for generation capacity expansion etc. As a result market participants are exposed to price and volume risk, which has led to the development of risk management practices. This paper provides an overview of risk management practices by market participants in electricity markets using financial derivatives.

Keywords: financial derivatives, forward, futures, options, risk management

Procedia PDF Downloads 456

Authors: Pao-Huei Chen, Shu-Mei Lin, Yih-Ming Weng, Zer-Ran Yu, Be-Jen Wang

Abstract:

Pancreatic α-amylase and intestinal α-glucosidase are the critical enzymes for the breakdown of complex carbohydrates into di- or mono-saccharide, which play an important role in modulating postprandial blood sugars. Angiotensin converting enzyme (ACE) converts inactive angiotensin-I into active angiotensin-II, which subsequently increase blood pressure through triggering vasoconstriction and aldosterone secretion. Thus, inhibition of carbohydrate-digestion enzymes and ACE will help the management of blood glucose and blood pressure, respectively. Studies showed Pleurotus citrinopileatus (PC), an edible mushroom and commonly cultured in oriental countries, exerted anticancer, immune improving, antioxidative, hypoglycemic and hypolipidemic effects. Previous studies also showed various molecular weights (MW) fractioned from extracts may affect biological activities due to varying contents of bioactive components. Thus, the objective of this study is to investigate the in vitro antioxidant, hypoglycemic and hypotenstive effects and distribution of active compounds of various MWs of cold water extract from P. citrinopileatus (CWEPC). CWEPC was fractioned into four various MW fractions, PC-I (＜1 kDa), PC-II (1-3.5 kDa), PC-III (3.5-10 kDa), and PC-IV (＞10 kDa), using an ultrafiltration system. The physiological activities, including antioxidant activities, the inhibition capabilities of pancreatic α-amylase, intestinal α-glucosidase, and hypertension-linked ACE, and the active components, including polysaccharides, protein, and phenolic contents, of CWEPC and four fractions were determined. The results showed that fractions with lower MW exerted a higher antioxidant activity (p<0.05), which was positively correlated to the levels of total phenols. In contrast, the inhibition effects on the activities of α-amylase, α-glucosidase, and ACE of PC-IV fraction were significantly higher than CWEPC and the other three low MW fractions (< 10 kDa), which was more related to protein contents. The inhibition capability of CWEPC and PC-IV on α-amylase activity was 1/13.4 to 1/2.7 relative to that of acarbose (positive control), respectively. However, the inhibitory ability of PC-IV on α-glucosidase (IC50 = 0.5 mg/mL) was significantly higher than acarbose (IC50 = 1.7 mg/mL). Kinetic data revealed that PC-IV fraction followed a non-competitive inhibition on α-glucosidase activity. In conclusion, the distribution of various bioactive components contribute to the functions of different MW fractions on oxidative stress prevention, and blood pressure and glucose modulation.

Keywords: α-Amylase, angiotensin converting enzyme, α-Glucosidase, Pleurotus citrinopileatus

Procedia PDF Downloads 446

Authors: Akhtar Aman, Abida Raza, Shumaila Bashir, Mehboob Alam

Abstract:

The development of efficient delivery systems remains a major concern in cancer chemotherapy as many efficacious anticancer drugs are hydrophobic and difficult to formulate. Nanomedicines based on drug-loaded amphiphilic glycol chitosan micelles offer potential advantages for the formulation of drugs such as etoposide that may improve the pharmacokinetics and reduce the formulation-related adverse effects observed with current formulations. Amphiphilic derivatives of glycol chitosan were synthesized by chemical grafting of palmitic acid N-hydroxysuccinimide and quaternization to glycol chitosan backbone. To this end, a 7.9 kDa glycol chitosan was modified by palmitoylation and quaternization, yielding a 13 kDa amphiphilic polymer. Micelles prepared from this amphiphilic polymer had a size of 162nm and were able to encapsulate up to 3 mg/ml etoposide. Pharmacokinetic results indicated that the GCPQ micelles transformed the biodistribution pattern and increased etoposide concentration in the brain significantly compared to free drugs after intravenous administration. AUC 0.5-24h showed statistically significant difference in ETP-GCPQ vs. Commercial preparation in liver (25 vs.70, p<0.001), spleen (27 vs.36, p<0.05), lungs (42 vs.136,p<0.001),kidneys(25 vs.70,p< 0.05),and brain(19 vs.9,p<0.001). ETP-GCPQ crossed the blood-brain barrier, and 4, 3.5, 2.6, 1.8, 1.7, 1.5, and 2.5 fold higher levels of etoposide were observed at 0.5, 1, 2, 4, 6, 12, and 24hrs; respectively suggesting these systems could deliver hydrophobic anticancer drugs such as etoposide to tumors but also increased their transport through the biological barriers, thus making it a good delivery system

Keywords: glycol chitosan, micelles, pharmacokinetics, tissue distribution

Procedia PDF Downloads 90

Authors: Jasneet Kaur, Swapandeep Singh Chimni

Abstract:

The unfavorable use of metal-based catalysts that are often extortionate and toxic can be overcome by using small organic molecules known as organocatalysts. A variety of small organic molecules, including Brønsted/Lewis bases and acids, based on sulfonic acids, phosphoric acids, amines, phosphines or carbenes, Cinchona alkaloids, have been used as organocatalysts. One of the key reasons for using organocatalysis is their ability to be effectively removed from the final product in comparison to the metallic counterparts, which are exceedingly difficult to remove. The present investigation seeks to explore the catalytic nature of Cinchona alkaloids as an organocatalyst for enantioselective synthesis of 3-substituted-3-aminooxindole, which is known to exhibit a variety of biological activities and pharmacological activities. In this context, an organocatalytic asymmetric route for the synthesis of 3-aminooxindoles via reaction of isatin imine with α-acetoxy-β-ketoesters has been developed. The bifunctional Cinchona derived thiourea catalyzed the reaction of α-acetoxy-β-ketoesters derivatives with isatin imine to afford 3-substituted-aminooxindole derivatives in up to 93% yield, 95% enantiomeric excess and >20:1 diastereomeric ratio. The reaction was performed at room temperature for two hours using 10 mol% of catalyst, in the presence of 4Å molecular sieves in tetrahydrofuran as a solvent at ambient temperature. After the completion of the reaction, the pure product could be easily separated by using column chromatography using hexane and ethyl acetate as solvents. In conclusion, the catalytic potential of Cinchona derived chiral thiourea-tertiary amine catalyst was explored for an organocatalytic enantioselective Mannich reaction of β-ketoester derivatives with various isatin imine derivatives under mild conditions.

Keywords: asymmetric synthesis, aminooxindoles, enantioselective, isatin imine

Procedia PDF Downloads 98

Authors: Sara Torabi, Sadegh Khazalpour, Mahdi Jamshidi

Abstract:

Nitro aromatic compounds are valuable materials because of their applications in the preparation of chemical intermediates for the synthesis of dyes, plastics, perfumes, energetic materials, and pharmaceuticals. Chemical and electrochemical procedures are reported for nitration of aromatic compounds. Flavonoid derivatives are present in many vegetables and fruits and are constituent of many common pharmaceuticals and dietary supplements. Electrochemistry provides very versatile means for the electrosynthesis, mechanistic and kinetic studies. To the best of our knowledge, and despite the importance of these compounds in numerous scientific fields, there are no reports on the electrochemical nitration of Quercetin derivatives. Herein, we describe a green electrochemical synthesis of a nitro compound. In this work, electrochemical oxidation of Quercetin has been studied in the presence of nitrite ion as a nucleophile in acetate buffer solution (c = 0.2 M, pH = 6.0), by means of cyclic voltammetry and controlled-potential coulometry. The results indicate the participation of produced o-benzoquinones in Michael reaction with nitrite ion (in the divided cell) to form the corresponding nitro diol (EC mechanism). The purity of product and characterization was done using ¹H NMR, ¹³C NMR, FTIR spectroscopic techniques. The presented strategies use a water/ethanol mixture as solvent. Ethanol as cosolvent was also used in the previous studies because of its low cost, safety, easy availability, recyclability, bioproductability, and biodegradability. These strategies represent a one-pot and facile process for the synthesis of nitro compound in high yield and purity under green conditions.

Keywords: electrochemical synthesis, green chemistry, cyclic voltammetry, molecular docking

Procedia PDF Downloads 123

Authors: Nagwa Mourad Abdelazeem, Marwa El-hussieny

Abstract:

Multicomponent reactions (MCRs), one-pot reactions form products from more than two different starting compounds. (MCRs) are ideal reaction systems leading to high structural diversity and molecular complexity through a single transformation. (MCRs) have a lot of advantage such as higher yield, less waste generation, use of readily available starting materials and high atom. (MCRs) provide a rapid process for efficient synthesis of key structures in discovery of drug on the other hand silica sulfuric acid (SSA) has been used as an efficient heterogeneous catalyst for many organic transformations. (SSA) is low cost, ease of preparation, catalyst recycling, and ease of handling, so in this article we used 2-(thiophen-2-yl)-1H-indole, N-substituted anilines and aldehyde in the presence of silica sulfuric acid (SSA) as a catalyst in water as solvent at room temperature to prepare 3,3'-(phenylmethylene)bis(2-(thiophen-2-yl)-1H-indole) and N-methyl-4-(phenyl(2-(thiophen-2-yl)-1H-indol-3-yl)methyl)aniline derivatives Via one-pot reaction. Compound 2-(thiophen-2-yl)-1H-indole belongs to the ubiquitous class of indoles which enjoy broad synthetic, biological and industrial applications ]. Cancer is considered the first or second most common reason of death all through the world. So the synthesized compounds will be tested as anticancer. We expected the synthesized compounds will give good results comparison to the reference drug.

Keywords: aldehydes, aza-friedel-crafts reaction, indole, multicomponent reaction

Procedia PDF Downloads 74

Authors: S. Ahmed John

Abstract:

Marine forms-bacteria, actinobacteria, cynobacteria, fungi, microalgae, seaweeds mangroves and other halophytes an extremely important oceanic resources and constituting over 90% of the oceanic biomass. The marine natural products have lead to the discovery of many compounds considered worthy for clinical applications. The marine sources have the highest probability of yielding natural products. Natural derivatives play an important role to prevent the cancer incidences as synthetic drug transformation in mangrove. 28.12% of anticancer compound extracted from the mangroves. Exchocaria agollocha has the anti cancer compounds. The present investigation reveals the potential of the Exchocaria agollocha with biotechnological applications for anti cancer, antimicrobial drug discovery, environmental remediation, and developing new resources for the industrial process. The anti-cancer activity of Exchocaria agollocha was screened from 3.906 to 1000 µg/ml of concentration with the dilution leads to 1:1 to 1:128 following methanol and chloroform extracts. The cell viability in the Exchocaria agollocha was maximum at the lower concentration where as low at the higher concentration of methanol and chloroform extracts when compare to control. At 3.906 concentration, 85.32 and 81.96 of cell viability was found at 1:128 dilution of methanol and chloroform extracts respectively. At the concentration of 31.25 following 1:16 dilution, the cell viability was 65.55 in methanol and 45.55 in chloroform extracts. However, at the higher concentration, the cell viability 22.35 and 8.12 was recorded in the extracts of methanol and chloroform. The cell viability was more in methanol when compare to chloroform extracts at lower concentration. The present findings gives current trends in screening and the activity analysis of metabolites from mangrove resources and to expose the models to bring a new sustain for tackling cancer. Bioactive compounds of Exchocaria agollocha have extensive use in treatment of many diseases and serve as a compound and templates for synthetic modification.

Keywords: bio-active product, compounds, natural products and microalgae

Procedia PDF Downloads 230

Authors: Shazia Mannan, Zunera Khalid, Hammad-Ul-Mubeen

Abstract:

Wingless type Mouse mammary tumor virus (MMTV) Integration site-10B (Wnt10B) is an important member of the Wnt protein family that functions as cellular messenger in paracrine manner. Aberrant Wnt10B activity is the cause of several abnormalities including cancers of breast, cervix, liver, gastric tract, esophagus, pancreas as well as physiological problems like obesity, and osteoporosis. The objective of this study was to determine the possible inhibitors against aberrant expression of Wnt10B in order to prevent and treat the physiological disorders associated with it. Wnt10B3D structure was predicted by using comparative modeling and then analyzed by PROCHECK, Verify3D, and Errat. The model having 84.54% quality value was selected and acylated to satisfy the hydrophobic nature of Wnt10B. For search of inhibitors, virtual screening was performed on Natural Products (NP) database. The compounds were filtered and ligand-based screening was performed using the antagonist for mouse Wnt-3A. This resulted in a library of 272 unique compounds having most potent drug like activities for Wnt-4. Out of the 271 molecules analyzed three small molecules ZINC35442871, ZINC85876388, and ZINC00754234 having activity against Wnt4 abbarent expression were found common through docking experiment of Wnt10B. It is concluded that the three molecules ZINC35442871, ZINC85876388, and ZINC00754234 can be considered as lead compounds for performing further drug designing experiments against aberrant Wnt expressions.

Keywords: Wnt10B inhibitors, comparative computational studies, proto-oncogene, molecular docking

Procedia PDF Downloads 137

Authors: Mthokozisi Simelane

Abstract:

Background: Malaria remains a life-threatening disease in tropical regions despite the advances in the treatment of this disease, it still remains a significant burden as some parasites have become resistant to the currently available drugs. This has created a necessity for the development of alternative, more efficient antimalarial drugs. Warburgia salutaris is a traditional medicinal plant used in malaria treatment by Zulu traditional healers. Materials and methods: The W. salutaris stem-bark was extracted with dichloromethane and the compound was isolated through column chromatography. The compound was identified and characterized by spectroscopic analysis (1H NMR, 13C NMR, IR and MS) and the structure was also confirmed by x-ray crystallography. The anti-plasmodial activity (in vitro) was studied on NF54 Plasmodium falciparum strain (CQS). Cytotoxicity was measured using the MTT assay on HEK239 and HEPG2 cell lines. Docking of Mukaadial acetate was conducted in AutoDock Vina. Structural modifications were conducted in UCSF Chimera and molecular interactions examined in LigPlot. Results: The compound, Mukaadial Acetate showed appreciable inhibition (IC50 0.44±0.10 µg/ml) of the parasite growth and cytotoxicity activity of 0.124±0.109 and 0.199±0.083 (µg/ml) on HEK293 and HEPG2 cells respectively. Molecular docking revealed that Mukaadial Acetate binds to the purine, pyrophosphate and ribose binding sites of the PfHGXPRT with an optimum binding conformation and forms hydrogen bond, steric and hydrophobic interactions with the residues inhabiting the respective binding sites. Conclusion: It is apparent that W. salutaris contains components (including Mukaadial Acetate) that exhibit antimalarial activity. This study scientifically validates the use of this plant in folk medicine.

Keywords: plasmodium falciparum, molecular docking, antimalarial activity, PfHGXPRT, Warburgia salutaris, mukaadial acetate

Procedia PDF Downloads 184

Authors: Rajandeep Kaur, Rajeev Gupta

Abstract:

Background: Chronic myeloid leukemia (CML) is the most common leukaemia in India. The annual incidence of chronic myeloid leukemia in India was originally reported to be 0.8 to 2.2 per 1,00,000 population. CML is a clonal disorder that is usually easily diagnosed because the leukemic cells of more than 95% of patients have a distinctive cytogenetic abnormality, the Philadelphia chromosome (Ph1). The approval of tyrosine kinase inhibitors (TKIs), which target BCR-ABL1 kinase activity, has significantly reduced the mortality rate associated with chronic myeloid leukemia (CML) and revolutionized treatment. Material and Methods: 80 diagnosed cases of CML were taken. Investigations were done. Bone marrow and molecular studies were also done and with EUTOS, patients were stratified into low and high-risk groups and then treatment with Imatinib was given to all patients and the molecular response was evaluated at 6 months and 12 months follow up with BCR-ABL by RT-PCR quantitative assay. Results: In the study population, out of 80 patients in the study population, 40 were females and 40 were males, with M: F is 1:1. Out of total 80 patients’ maximum patients (54) were in 31-60 years age group. Our study showed a most common symptom of presentation is abdominal discomfort followed by fever. Out of the total 80 patients, 25 (31.3%) patients had high EUTOS scores and 55 (68.8%) patients had low EUTOS scores. On 6 months follow up 36.3% of patients had Complete Molecular Response, 16.3% of patients had Major Molecular Response and 47.5% of patients had No Molecular Response but on 12 months follow up 71.3% of patients had Complete Molecular Response, 16.25% of patients had Major Molecular Response and 12.5% patients had No Molecular Response. Conclusion: In this study, we found a significant correlation between EUTOS score and Molecular response at 6 months and 12 months follow up after Imatinib therapy.

Keywords: chronic myeloid leukemia, European treatment and outcome study score, hematological response, molecular response, tyrosine kinase inhibitor

Procedia PDF Downloads 84

Authors: Uftah Ali M. Shushni, Viola Stuppec, Ulrike Lindequist

Abstract:

Because of the evolving resistance of microorganisms to existing antibiotics, there is an increasing need for new antibiotics not only in human but also in veterinary medicine. As part of our ongoing work on the secondary metabolites produced by marine fungi, the organic extract of the culture filtrate of an Ascomycetous fungus, which was found on driftwood collected from the coast of the Greifswalder Bodden, Baltic Sea, Germany displayed antimicrobial activity against some fish and human pathogenic bacteria. Bioactivity-guided column chromatographic separation led to the isolation of 6-Deoxybostrycoidin. The structure was determined from the interpretation of spectroscopic data (UV, MS, and NMR). 6-Deoxybostrycoidin exhibited in vitro activity against Bacillus subtilis, Staphylococcus aureus and Flexibacter maritimus with minimal inhibitory concentrations of 25, 12.5 and 12.5 μg/ml respectively.

Keywords: marine fungi, fish pathogenic bacteria, microorganism, medicine

Procedia PDF Downloads 508

Authors: Marianna Maiaru, Gregory M. Odegard, Josh Kemppainen, Ivan Gallegos, Michael Olaya

Abstract:

Ceramic matrix composites (CMCs) are typically used in applications that require long-term mechanical integrity at elevated temperatures. CMCs are usually fabricated using a polymer precursor that is initially polymerized in situ with fiber reinforcement, followed by a series of cycles of pyrolysis to transform the polymer matrix into a rigid glass or ceramic. The pyrolysis step typically generates volatile gasses, which creates porosity within the polymer matrix phase of the composite. Subsequent cycles of monomer infusion, polymerization, and pyrolysis are often used to reduce the porosity and thus increase the durability of the composite. Because of the significant expense of such iterative processing cycles, new generations of CMCs with improved durability and manufacturability are difficult and expensive to develop using standard Edisonian approaches. The goal of this research is to develop a computational process-modeling-based approach that can be used to design the next generation of CMC materials with optimized material and processing parameters for maximum strength and efficient manufacturing. The process modeling incorporates computational modeling tools, including molecular dynamics (MD), to simulate the material at multiple length scales. Results from MD simulation are used to inform the continuum-level models to link molecular-level characteristics (material structure, temperature) to bulk-level performance (strength, residual stresses). Processing parameters are optimized such that process-induced residual stresses are minimized and laminate strength is maximized. The multiscale process modeling method developed with this research can play a key role in the development of future CMCs for high-temperature and high-strength applications. By combining multiscale computational tools and process modeling, new manufacturing parameters can be established for optimal fabrication and performance of CMCs for a wide range of applications.

Keywords: digital engineering, finite elements, manufacturing, molecular dynamics

Procedia PDF Downloads 81

Authors: Sayanti Kar, Amitava Ghosh, Pritam Aitch, Gupinath Bhandari

Abstract:

An extensive seasonal analysis of wastewater had been done from outfalls of river Ganga in Howrah, Hooghly, 24 PGS (N) District, West Bengal, India during 2017. The morphological parameters of Bitter gourd (Momordica charantia L.) were estimated under wastewater treatment. An approach to study the activity within the range of low molecular weight peptide 3-0.5 kDa were taken through its extraction and purification by ion exchange resin column, cation, and anion exchanger. HPLC analysis had been done for both in wastewater treated and untreated plants. The antioxidant activity by using DPPH and germination percentage in control and treated plants were also determined in relation to wastewater effect. The inhibition of growth and its parameters were maximum in pre-monsoon in comparing to post-monsoon and monsoon season. The study also helped to explore the effect of wastewater on the peptidome of Bitter gourd (Momordica charantia L.). Some of these low molecular weight peptide(s) (3-0.5 kDa) also inhibited during wastewater treatment. Expression of particular peptide(s) or absence of some peptide(s) in chromatogram indicated the adverse effects on plants which may be the indication of stressful condition. Pre monsoon waste water was found to create more impact than other two.

Keywords: bitter gourd (Momordica charantia l.), low molecular weight peptide, river ganga, waste water

Procedia PDF Downloads 107

Authors: Rahul Shrivastava, Manish Tripathi, Mohmmad Yasir, Shailesh Singh

Abstract:

Life style changes and depletion in atmospheric ozone layer in recent decades lead to increase in skin cancer including both melanoma and nonmelanomas. Natural products which were obtained from different plant species have the potential of anti skin cancer activity. In regard of this, present study focuses the potential effect of Glycosmis pentaphylla against anti skin cancer activity. Different Phytochemical constituents which were present in the roots of Glycosmis pentaphylla were identified and were used as ligands after sketching of their structures with the help of ACD/Chemsketch. These ligands are screened for their anticancer potential with proteins which are involved in skin cancer effects with the help of pyrx software. After performing docking studies, results reveal that Noracronycine secondary metabolite of Glycosmis pentaphylla shows strong affinity of their binding energy with Ribosomal S6 Kinase 2 (2QR8) protein. Ribosomal S6 Kinase 2 (2QR8) has an important role in the cell proliferation and transformation mediated through by N-terminal kinase domain and was induced by the tumour promoters such as epidermal growth factor. It also plays a key role in the neoplastic transformation of human skin cells and in skin cancer growth. Noracronycine interact with THR-493 and MET-496 residue of Ribosomal S6 Kinase 2 protein with binding energy ΔG = -8.68 kcal/mole. Thus on the basis of this study we can say that Noracronycine which present in roots of Glycosmis pentaphylla can be used as lead compound against skin cancer.

Keywords: glycosmis pentaphylla, pyrx, ribosomal s6 kinase, skin cancer

Procedia PDF Downloads 286

Authors: E. G. Zaki, M. A. Migahed, A. M. Al-Sabagh, E. A. Khamis

Abstract:

Inhibition effect of four novel nonionic surfactants based on sulphonamide, of linear alkyl benzene sulphonic acid (LABS), was reacted with 1 mole triethylenetetramine, tetraethylenepentamine then Ethoxylation of amide X 65 type carbon steel in oil wells formation water under H2S environment was investigated by electrochemical measurements. Scanning electron microscopy (SEM) and energy dispersion X-ray (EDX) were used to characterize the steel surface. The results showed that these surfactants act as a corrosion inhibitor in and their inhibition efficiencies depend on the ethylene oxide content in the system. The obtained results showed that the percentage inhibition efficiency (η%) was increased by increasing the inhibitor concentration until the critical micelle concentration (CMC) reached The quantum chemistry calculations were carried out to study the molecular geometry and electronic structure of obtained derivatives. The energy gap between the highest occupied molecular orbital and lowest unoccupied molecular orbital has been calculated using the theoretical computations to reflect the chemical reactivity and kinetic stability of compounds.

Keywords: corrosion, surfactants, steel surface, quantum

Procedia PDF Downloads 344

Authors: Madhusudan Purohit, Stephen Philip, Bharathkumar Inturi

Abstract:

In this paper we report the quantitative structure activity relationship of novel bis-triazole derivatives for predicting the activity profile. The full model encompassed a dataset of 46 Bis- triazoles. Tripos Sybyl X 2.0 program was used to conduct CoMSIA QSAR modeling. The Partial Least-Squares (PLS) analysis method was used to conduct statistical analysis and to derive a QSAR model based on the field values of CoMSIA descriptor. The compounds were divided into test and training set. The compounds were evaluated by various CoMSIA parameters to predict the best QSAR model. An optimum numbers of components were first determined separately by cross-validation regression for CoMSIA model, which were then applied in the final analysis. A series of parameters were used for the study and the best fit model was obtained using donor, partition coefficient and steric parameters. The CoMSIA models demonstrated good statistical results with regression coefficient (r2) and the cross-validated coefficient (q2) of 0.575 and 0.830 respectively. The standard error for the predicted model was 0.16322. In the CoMSIA model, the steric descriptors make a marginally larger contribution than the electrostatic descriptors. The finding that the steric descriptor is the largest contributor for the CoMSIA QSAR models is consistent with the observation that more than half of the binding site area is occupied by steric regions.

Keywords: 3D QSAR, CoMSIA, triazoles, novel heterocycles

Procedia PDF Downloads 428