Search results for: curcumin analogues

Authors: Enrico Gugliandolo, Salvatore Cuzzocrea, Rosalia Crupi

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Osteoarthritis (OA) is one of the most common chronic pain conditions in dogs and cats. OA pain is currently viewed as a mixed phenomenon involving both inflammatory and neuropathic mechanisms at the peripheral (joint) and central (spinal and supraspinal) levels. Oxidative stress has been implicated in OA pain. Although nonsteroidal anti-inflammatory drugs are commonly prescribed for OA pain, they should be used with caution in pets because of adverse effects in the long term and controversial efficacy on neuropathic pain. An unmet need remains for safe and effective long-term treatments for OA pain. Palmitoyl-glucosamine (PGA) is an analogue of the ALIAamide palmitoylethanolamide, i.e., a body’s own endocannabinoid-like compound playing a sentinel role in nociception. PGA, especially in the micronized formulation, was shown safe and effective in OA pain. The aim of this study was to investigate the effect of a co-micronized formulation of PGA with the natural antioxidant curcumin (PGA-cur) on OA pain. Ten Sprague-Dawley male rats were used for each treatment group. The University of Messina Review Board for the care and use of animals authorized the study. On day 0, rats were anesthetized (5.0% isoflurane in 100% O2) and received intra-articular injection of MIA (3 mg in 25 μl saline) in the right knee joint, with the left being injected an equal volume of saline. Starting the third day after MIA injection, treatments were administered orally three times per week for 21 days, at the following doses: PGA 20 mg/kg, curcumin 10 mg/kg, PGA-cur (2:1 ratio) 30 mg/kg. On day 0 and 3, 7, 14 and 21 days post-injection, mechanical allodynia was measured using a dynamic plantar Von Frey hair aesthesiometer and expressed as paw withdrawal threshold (PWT) and latency (PWL). Motor functional recovery of the rear limb was evaluated on the same time points by walking track analysis using the sciatic functional index. On day 21 post-MIA injection, the concentration of the following inflammatory and nociceptive mediators was measured in serum using commercial ELISA kits: tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), nerve growth factor (NGF) and matrix metalloproteinase-1-3-9 (MMP-1, MMP-3, MMP-9). The results were analyzed by ANOVA followed by Bonferroni post-hoc test for multiple comparisons. Micronized PGA reduced neuropathic pain, as shown by the significant higher PWT and PWL values compared to vehicle group (p < 0.0001 for all the evaluated time points). The effect of PGA-cur was superior at all time points (p < 0.005). PGA-cur restored motor function already on day 14 (p < 0.005), while micronized PGA was effective a week later (D21). MIA-induced increase in the serum levels of all the investigated mediators was inhibited by PGA-cur (p < 0.01). PGA was also effective, except on IL-1 and MMP-3. Curcumin alone was inactive in all the experiments at any time point. The encouraging results suggest that PGA-cur may represent a valuable option in OA pain management and warrant further confirmation in well-powered clinical trials.

Keywords: ALIAmides, curcumin, osteoarthritis, palmitoyl-glucosamine

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Authors: Jyh-Ping Chen, Yu-Tin Lai

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Wound healing is a complicated process involving overlapping hemostasis, inflammation, proliferation, and maturation phases. Ideal wound dressings can replace native skin functions in full thickness skin wounds through faster healing rate and also by reducing scar formation. Poly(lactic-co-glycolic acid) (PLGA) is an U.S. FDA approved biodegradable polymer to be used as ideal wound dressing material. Several in vitro and in vivo studies have demonstrated the effectiveness of curcumin in decreasing the release of inflammatory cytokines, inhibiting enzymes associated with inflammations, and scavenging free radicals that are the major cause of inflammation during wound healing. Heparin has binding affinities to various growth factors. With the unique and beneficial features offered by those molecules toward the complex process of wound healing, we postulate a composite wound dressing constructed from PLGA, curcumin and heparin would be a good candidate to accelerate scarless wound healing. In this work, we use electrospinning to prepare curcumin-loaded aligned PLGA nanofibrous membranes (PC NFMs). PC NFMs were further subject to oxygen plasma modification and surfaced-grafted with heparin through carbodiimide-mediated covalent bond formation to prepare curcumin-loaded PLGA-g-heparin (PCH) NFMs. The nanofibrous membranes could act as three-dimensional scaffolds to attract fibroblast migration, reduce inflammation, and increase wound-healing related growth factors concentrations at wound sites. From scanning electron microscopy analysis, the nanofibers in each NFM are with diameters ranging from 456 to 479 nm and with alignment angles within  0.5°. The NFMs show high tensile strength and good water absorptivity and provide suitable pore size for nutrients/wastes transport. Exposure of human dermal fibroblasts to the extraction medium of PC or PCH NFM showed significant protective effects against hydrogen peroxide than PLGA NFM. In vitro wound healing assays also showed that the extraction medium of PCH NFM showed significantly better migration ability toward fibroblasts than PC NFM, which is further better than PLGA NFM. The in vivo healing efficiency of the NFMs was further evaluated by a full thickness excisional wound healing diabetic rat model. After 14 days, PCH NFMs exhibits 86% wound closure rate, which is significantly different from other groups (79% for PC and 73% for PLGA NFM). Real-time PCR analysis indicated PC and PCH NFMs down regulated anti-oxidative enzymes like glutathione peroxidase (GPx) and superoxide dismutase (SOD), which are well-known transcription factors involved in cellular inflammatory responses to stimuli. From histology, the wound area treated with PCH NFMs showed more vascular lumen formation from immunohistochemistry of α-smooth muscle actin. The wound site also had more collagen type III (65.8%) expression and less collagen type I (3.5%) expression, indicating scar-less wound healing. From Western blot analysis, the PCH NFM showed good affinity toward growth factors from increased concentration of transforming growth factor-β (TGF-β) and fibroblast growth factor-2 (FGF-2) at the wound site to accelerate wound healing. From the results, we suggest PCH NFM as a promising candidate for wound dressing applications.

Keywords: Curcumin, heparin, nanofibrous membrane, poly(lactic-co-glycolic acid) (PLGA), wound dressing

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Authors: Sunil Kumar

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For many years, small organic molecules derived naturally from microbes and plants have delivered a number of expedient therapeutic drug agents. The search for naturally occurring lead compounds has continued in recent years as well, with the constituents of marine flora and fauna along with those of telluric microorganisms and plants being investigated for their anti-bacterial and anti-cancer activities. It has been observed that such promising lead molecules incline to promptly generate substantial attention among scientists like synthetic organic chemists and biologists. Subsequently, the availability of a given precious natural product sample may be enriched, and it may be possible to determine a preliminary idea of structure-activity relationships to develop synthetic analogues. For instance, anti-tumor drug topotecan is a synthetic chemical compound similar in chemical structure to camptothecin which is found in extracts of Camptotheca acuminate. Similarly, researchers at AstraZeneca discovered anti-biotic pyrrolamide through a fragment-based lead generation approach from kibdelomycin, which is isolated from Staphylococcus aureuss.

Keywords: anticancer, antibiotic, lead molecule, natural product, synthetic analogues

Procedia PDF Downloads 123

Authors: Drashti G. Daraji, Rosa E. Moo-Puc, Hitesh D. Patel

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Substituted 2-Thioimidazole analogues have been synthesized and confirmed by advanced spectroscopic techniques. Among them, ten compounds have been selected and evaluated for their in vitro anti-cancer activity at the National Cancer Institute (NCI) for testing against a panel of 60 different human tumor cell lines derived from nine neoplastic cancer types. Furthermore, synthesized compounds were tested for their in vitro antiprotozoal activity, and none of them exhibited significant potency against antiprotozoans. It was observed that the tested all compounds seem effective on the UACC-62 melanoma cancer cell line as compared to other cancer cell lines and also exhibited the least potent in the Non-Small Cell Lung Cancer cell line in one-dose screening. In silico studies of these derivatives were carried out by molecular docking techniques and Absorption, Distribution, Metabolism, and Excretion (ADME) using Schrödinger software to find potent B-Raf kinase inhibitor (PDB ID: 3OG7). All the compounds have been performed for docking study; Compound D4 has a good docking score for melanoma cancer as compared with other.

Keywords: anticancer activity, cancer cell line, 2-thio imidazole, one-dose assay, molecular docking

Procedia PDF Downloads 115

Authors: Eddy Neuhaus, Hanif Shirinzadeh, Cigdem Karaaslan, Elif Ince, Hande Gurer-Orhan, Sibel Suzen

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Reactive oxygen species (ROS) and oxidative stress can cause fatal damage to essential cell structures, including DNA. It is known that use of antioxidants could be advantageous in the prevention of various diseases such as cancer, cardiovascular diseases and neurodegenerative disorders. Since antioxidant properties of the indole ring-containing melatonin (MLT) has been described and evaluated, MLT-related compounds such as MLT metabolites and synthetic analogues are under investigation to determine which exhibit the highest activity with the lowest side-effects. Owing to indole and hydrazones appealing physiological properties and are mostly found in numerous biologically active compounds a series of indole-7-carbaldehyde hydrazone derivatives were synthesized, characterized and in vitro antioxidant activity was investigated by evaluating their reducing effect against oxidation of a redox-sensitive fluorescent probe. Cytotoxicity potential of all indole-based MLT analogues was investigated both by lactate dehydrogenase leakage assay and by MTT assay. This work was supported by The Scientific and Technological Research Council of Turkey (TÜBİTAK) Research and Development Grant 112S599.

Keywords: melatonin, antioxidant activity, indole, hydrazone, oxidative stress

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Authors: Souad Mouzaoui, Bahia Djerdjouri

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Oxidative stress is one of the main factors involved in the onset and chronicity of inflammatory bowel disease (IBD). In this study, we investigated the beneficial effects of a potent natural antioxidant, curcumin (Cur) on colitis and mitochondrial dysfunction in trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. Rectal instillation of the chemical irritant TNBS (30 mg kg-1) induced the disruption of distal colonic architecture and a massive inflammatory cells influx to the mucosa and submucosa layers. Under these conditions, daily administration of Cur (25 mg kg-1) efficiently decreased colitis scores in the inflamed distal colon by reducing leukocyte infiltrate as attested by reduced myeloperoxidase (MPO) activity. Moreover, the levels of nitrite, an end product of inducible NO synthase activity (iNOS) and malonyl dialdehyde (MDA), a marker of lipid peroxidation increased in a time depending manner in response to TNBS challenge. Conversely, the markers of the antioxidant pool, reduced glutathione (GSH) and catalase activity (CAT) were drastically reduced. Cur attenuated oxidative stress markers and partially restored CAT and GSH levels. Moreover, our results expanded the effect of Cur on TNBS-induced colonic mitochondrial dysfunction. In fact, TNBS induced mitochondrial swelling and lipids peroxidation. These events reflected in the opening of mitochondrial transition pore and could be an initial indication in the cascade process leading to cell death. TNBS inhibited also mitochondrial respiratory activity, caused overproduction of mitochondrial superoxide anion (O2-.) and reduced level of mitochondrial GSH. Nevertheless, Cur reduced the extent of mitochondrial oxidative stress induced by TNBS and restored colonic mitochondrial function. In conclusion, our results showed the critical role of oxidative stress in TNBS-induced colitis. They highlight the role of colonic mitochondrial dysfunction induced by TNBS, as a potential source of oxidative damages. Due to its potent antioxidant properties, Cur opens a promising therapeutic approach against oxidative inflammation in IBD.

Keywords: colitis, curcumin, mitochondria, oxidative stress, TNBS

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Authors: Ramalingam Boobalan, Chinpiao Chen, Jui-I. Chiao

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A series of erlotinib analogues that have structural modification at 6,7-alkoxyl positions is efficiently synthesized. The key reactions that involved in synthesis are one-pot oxime formation-dehydration for the formation of nitrile, quinazoline ring formation reaction between aniline and o-cyanoaniline via formamidine intermediate, Fe/NH4Cl catalyzed reduction-hetereocyclization-reductive ring opening reaction for the formation of o-aminobenzamide, high yielding seal tube reactions for O-demethylation, sodium iodide substitution, ammonia substitution. The in vitro anti-tumor activity of synthesized compounds is studied in two non-small cell lung cancer (NSCLC) cell lines (A549 and H1975). Among the synthesized compounds, the iodo compound 6 (ETN-6) exhibits higher anti-cancer activity compared to erlotinib. An efficient method is developed for the conjugation of erlotinib analogue-4, alcohol compound, with protein, bovine serum albumin (BSA), via succinic acid linker. The in vitro anti-tumor activity of the protein attached erlotinib analogue, 8 (ETN-4-Suc-BSA), showed stronger inhibitory activity in both A549 and H1975 NSCLC cell lines.

Keywords: anti-cancer, BSA, EGFR, Erlotinib

Procedia PDF Downloads 300

Authors: Numair A. Siddiqui, Usman Muhammad, Manoj J. Mathew, Ramkumar M., Benjamin Sautter, Muhammad A. K. El-Ghali, David Menier, Shiqi Zhang

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The sedimentological parameterization of shallow-marine siliciclastic reservoirs in terms of reservoir quality and heterogeneity from outcrop study can help improve the subsurface reservoir prediction. An architectural analysis has documented variations in sandstone geometry and rock properties within shallow-marine sandstone exposed in the Miocene Sandakan Formation of Sabah, Borneo. This study demonstrates reservoir sandstone quality assessment for subsurface rock evaluation, from well-exposed successions of the Sandakan Formation, Borneo, with which applicable analogues can be identified. The analyses were based on traditional conventional field investigation of outcrops, grain-size and petrographic studies of hand specimens of different sandstone facies and gamma-ray and permeability measurements. On the bases of these evaluations, the studied sandstone was grouped into three qualitative reservoir rock classes; high (Ø=18.10 – 43.60%; k=1265.20 – 5986.25 mD), moderate (Ø=17.60 – 37%; k=21.36 – 568 mD) and low quality (Ø=3.4 – 15.7%; k=3.21 – 201.30 mD) for visualization and prediction of subsurface reservoir quality. These results provided analogy for shallow marine sandstone reservoir complexity that can be utilized in the evaluation of reservoir quality of regional and subsurface analogues.

Keywords: architecture and sedimentology, subsurface rock evaluation, reservoir quality, borneo

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Authors: Ergun Sakalar, Kubra Bilgic

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In the last decades, real-time PCR has become a reliable tool preferred to use in many laboratories for pathogen detection. This technique allows for monitoring target amplification via fluorescent molecules besides admit of quantitative analysis by enabling of convert outcomes of thermal cycling to digital data. Sensitivity and traceability of real-time PCR are based on measuring of fluorescence that appears only when fluorescent reporter dye bound to specific target DNA.The fluorescent reporter systems developed for this purpose are divided into two groups. The first group consists of intercalator fluorescence dyes such as SYBR Green, EvaGreen which binds to double-stranded DNA. On the other hand, the second group includes fluorophore-labeled oligonucleotide probes that are separated into three subgroups due to differences in mechanism of action; initial primer-probes such as Cyclicons, Angler®, Amplifluor®, LUX™, Scorpions, and the second one hydrolysis probes like TaqMan, Snake assay, finally hybridization probes, for instance, Molecular Beacons, Hybprobe/FRET, HyBeacon™, MGB-Eclipse, ResonSense®, Yin-Yang, MGB-Pleiades. In addition nucleic acid analogues, an increase of probe affinity to target site is also employed with fluorescence-labeled probes. Consequently, abundant real-time PCR detection chemistries are chosen by researcher according to the field of application, mechanism of action, advantages, and proper structures of primer/probes.

Keywords: fluorescent dye, food safety, molecular probes, nucleic acid analogues

Procedia PDF Downloads 217

Authors: Sundaram Arulmozhiraja, Kanade Shimizu, Yuta Yamamoto, Satoshi Ichikawa, Maenaka Katsumi, Hiroaki Tokiwa

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Drug discovery is shifting from small molecule based drugs targeting local active site to middle molecules (MM) targeting large, flat, and groove-shaped binding sites, for example, protein-protein interface because at least half of all targets assumed to be involved in human disease have been classified as “difficult to drug” with traditional small molecules. Hence, MMs such as peptides, natural products, glycans, nucleic acids with various high potent bioactivities become important targets for drug discovery programs in the recent years as they could be used for ‘undruggable” intracellular targets. Cell membrane permeability is one of the key properties of pharmacodynamically active MM drug compounds and so evaluating this property for the potential MMs is crucial. Computational prediction for cell membrane permeability of molecules is very challenging; however, recent advancement in the molecular dynamics simulations help to solve this issue partially. It is expected that MMs with high membrane permeability will enable drug discovery research to expand its borders towards intracellular targets. Further to understand the chemistry behind the permeability of MMs, it is necessary to investigate their conformational changes during the permeation through membrane and for that their interactions with the membrane field should be studied reliably because these interactions involve various non-bonding interactions such as hydrogen bonding, -stacking, charge-transfer, polarization dispersion, and non-classical weak hydrogen bonding. Therefore, parameters-based classical mechanics calculations are hardly sufficient to investigate these interactions rather, quantum mechanical (QM) calculations are essential. Fragment molecular orbital (FMO) method could be used for such purpose as it performs ab initio QM calculations by dividing the system into fragments. The present work is aimed to study the cell permeability of middle molecules using molecular dynamics simulations and FMO-QM calculations. For this purpose, a natural compound syringolin and its analogues were considered in this study. Molecular simulations were performed using NAMD and Gromacs programs with CHARMM force field. FMO calculations were performed using the PAICS program at the correlated Resolution-of-Identity second-order Moller Plesset (RI-MP2) level with the cc-pVDZ basis set. The simulations clearly show that while syringolin could not permeate the membrane, its selected analogues go through the medium in nano second scale. These correlates well with the existing experimental evidences that these syringolin analogues are membrane-permeable compounds. Further analyses indicate that intramolecular -stacking interactions in the syringolin analogues influenced their permeability positively. These intramolecular interactions reduce the polarity of these analogues so that they could permeate the lipophilic cell membrane. Conclusively, the cell membrane permeability of various middle molecules with potent bioactivities is efficiently studied using molecular dynamics simulations. Insight of this behavior is thoroughly investigated using FMO-QM calculations. Results obtained in the present study indicate that non-bonding intramolecular interactions such as hydrogen-bonding and -stacking along with the conformational flexibility of MMs are essential for amicable membrane permeation. These results are interesting and are nice example for this theoretical calculation approach that could be used to study the permeability of other middle molecules. This work was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number 18ae0101047.

Keywords: fragment molecular orbital theory, membrane permeability, middle molecules, molecular dynamics simulation

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Authors: Elsie M. Nolte, Annie M. Joubert, Roy Lakier, Maryke Etsebeth, Jolene M. Helena, Marcel Verwey, Laurence Lafanechere, Anne E. Theron

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Treatment regimens for breast- and lung cancers may include both radiation- and chemotherapy. Ideally, a pharmaceutical agent which selectively sensitizes cancer cells to gamma (γ)-radiation would allow administration of lower doses of each modality, yielding synergistic anti-cancer benefits and lower metastasis occurrence, in addition to decreasing the side-effect profiles. A range of 2-methoxyestradiol (2-ME) analogues, namely 2-ethyl-3-O-sulphamoyl-estra-1,3,5 (10) 15-tetraene-3-ol-17one (ESE-15-one), 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol) and 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16) were in silico-designed by our laboratory, with the aim of improving the parent compound’s bioavailability in vivo. The main effect of these compounds is the disruption of microtubule dynamics with a resultant mitotic accumulation and induction of programmed cell death in various cancer cell lines. This in vitro study aimed to determine the cellular responses involved in the radiation sensitization effects of these analogues at low doses in breast- and lung cancer cell lines. The oestrogen receptor positive MCF-7-, oestrogen receptor negative MDA-MB-231- and triple negative BT-20 breast cancer cell lines as well as the A549 lung cancer cell line were used. The minimal compound- and radiation doses able to induce apoptosis were determined using annexin-V and cell cycle progression markers. These doses (cell line dependent) were used to pre-sensitize the cancer cells 24 hours prior to 6 gray (Gy) radiation. Experiments were conducted on samples exposed to the individual- as well as the combination treatment conditions in order to determine whether the combination treatment yielded an additive cell death response. Morphological studies included light-, fluorescence- and transmission electron microscopy. Apoptosis induction was determined by flow cytometry employing annexin V, cell cycle analysis, B-cell lymphoma 2 (Bcl-2) signalling, as well as reactive oxygen species (ROS) production. Clonogenic studies were performed by allowing colony formation for 10 days post radiation. Deoxyribonucleic acid (DNA) damage was quantified via γ-H2AX foci and micronuclei quantification. Amplification of the p53 signalling pathway was determined by western blot. Results indicated that exposing breast- and lung cancer cells to nanomolar concentrations of these analogues 24 hours prior to γ-radiation induced more cell death than the compound- and radiation treatments alone. Hypercondensed chromatin, decreased cell density, a damaged cytoskeleton and an increase in apoptotic body formation were observed in cells exposed to the combination treatment condition. An increased number of cells present in the sub-G1 phase as well as increased annexin-V staining, elevation of ROS formation and decreased Bcl-2 signalling confirmed the additive effect of the combination treatment. In addition, colony formation decreased significantly. p53 signalling pathways were significantly amplified in cells exposed to the analogues 24 hours prior to radiation, as was the amount of DNA damage. In conclusion, our results indicated that pre-treatment of breast- and lung cancer cells with low doses of 2-ME analogues sensitized breast- and lung cancer cells to γ-radiation and induced apoptosis more so than the individual treatments alone. Future studies will focus on the effect of the combination treatment on non-malignant cellular counterparts.

Keywords: cancer, microtubule dynamics, radiation therapy, radiosensitization

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Authors: Shiva Shakori Poshteh

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Lung cancer is a highly prevalent and devastating disease, representing a significant global health concern with profound implications for healthcare systems and society. Its high incidence, mortality rates, and late-stage diagnosis contribute to its formidable nature. To address these challenges, nanoparticle-based drug delivery has emerged as a promising therapeutic strategy. Curcumin (CUR), a natural compound derived from turmeric, has garnered attention as a potential nanomedicine for lung cancer treatment. Nanoparticle formulations of CUR offer several advantages, including improved drug delivery efficiency, enhanced stability, controlled release kinetics, and targeted delivery to lung cancer cells. CUR exhibits a diverse array of effects on cancer cells. It induces apoptosis by upregulating pro-apoptotic proteins, such as Bax and Bak, and downregulating anti-apoptotic proteins, such as Bcl-2. Additionally, CUR inhibits cell proliferation by modulating key signaling pathways involved in cancer progression. It suppresses the PI3K/Akt pathway, crucial for cell survival and growth, and attenuates the mTOR pathway, which regulates protein synthesis and cell proliferation. CUR also interferes with the MAPK pathway, which controls cell proliferation and survival, and modulates the Wnt/β-catenin pathway, which plays a role in cell proliferation and tumor development. Moreover, CUR exhibits potent antioxidant activity, reducing oxidative stress and protecting cells from DNA damage. Utilizing CUR as a standalone treatment is limited by poor bioavailability, lack of targeting, and degradation susceptibility. Nanoparticle-based delivery systems can overcome these challenges. They enhance CUR’s bioavailability, protect it from degradation, and improve absorption. Further, Nanoparticles enable targeted delivery to lung cancer cells through surface modifications or ligand-based targeting, ensuring sustained release of CUR to prolong therapeutic effects, reduce administration frequency, and facilitate penetration through the tumor microenvironment, thereby enhancing CUR’s access to cancer cells. Thus, nanoparticle-based CUR delivery systems promise to improve lung cancer treatment outcomes. This article provides an overview of lung cancer, explores CUR nanoparticles as a treatment approach, discusses the benefits and challenges of nanoparticle-based drug delivery, and highlights prospects for CUR nanoparticles in lung cancer treatment. Future research aims to optimize these delivery systems for improved efficacy and patient prognosis in lung cancer.

Keywords: lung cancer, curcumin, nanomedicine, nanoparticle-based drug delivery

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Authors: V. Yu. Volgutov, A. I. Orlova, S. A. Khainakov

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NaZr2(PO4)3 (NZP) and their structural analogues are characterized by a peculiar behaviors on heating – they have different expansion and contraction along different crystallographic directions due to specific arrangements of crystal structure in these compounds. An important feature of such structures is the ability to incorporate into their structural analogues wide variety of metal cations having different size and oxidation states, with different combinations and concentrations. These cations are located in different crystallographic non-equivalent positions of octahedral tetrahedral crystal framework as well as in inter-framework cavities. Through, due to iso- and hetero-valent isomorphism of the cations (and the anions) in NZP, it becomes possible to tuning the compositions and to obtain the compounds with ‘on a plan’ properties. For the design of compounds with low and ultra-low thermal expansion including those with tailored thermal expansion properties, the following crystallochemical principles it seems are promising: 1) Insertion into crystal M1 position the cations having different sizes and, 2) the variation in the composition of compounds, providing different occupation of crystal M1 position. Following these principles we have designed and synthesized the next NZP-type phosphates series: a) where radii of the cations in the M1 crystal position was varied: Zr1/4Zr2(PO4)3 - Th1/4Zr2(PO4)3 (series I); R1/3Zr2(PO4)3 where R= Nd, Eu, Er (series II), b) where the occupation of M1 crystal position was varied: Zr1/4Zr2(PO4)3-Er1/3Zr2(PO4)3 (series III) and Zr1/4Zr2(PO4)3-Sr1/2Zr2(PO4)3 (series IV). The thermal expansion parameters were determined over the range of 25-800ºC. For each series the minimum axial coefficient of thermal expansion αa = αb, αc and their anisotropy Δα = Iαa - αcI, 10-6 K-1 was found as next: -1.51, 1.07, 2.58 for Th1/4Zr2(PO4)3 (series I); -0.72, 0.10, 0.81 for Nd1/3Zr2(PO4)3 (series II); -2.78, 1.35, 4.12 for Er1/6Zr1/8Zr2(PO4)3 (series III); 2.23, 1.32, 0.91 for Sr1/2Zr2(PO4)3 (series IV). The measured tendencies of the thermal expansion of crystals were in good agreement with predicted ones. For one of the members from the studied phosphates namely Th1/16Zr3/16Zr2(PO4)3 structural refinement have been carried out at 25, 200, 600, and 800°C. The dependencies of the structural parameters with the temperature have been determined.

Keywords: high-temperature crystallography, NaZr2(PO4)3, (NZP) analogs, structural-chemical principles, tuning thermal expansion

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Authors: Pravin Mishra, Ajeet K. Jha, Pankaj K. Jha

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This technical note is aimed at providing a brief information on goat breeds, its breeding seasonality and different methods of oestrous synchronization for Nepalese goat farmers. It was observed that, these goats are seasonal breeder and showed oestrous during mainly two season; December- February and March-May. This leads to an irregular supply of goat to market and a wide variations in market price. Oestrus synchronization is only an alternative reproductive tool to overcome this scarcity by enhancing production and productivity. This technique enables goat producers breed their animals within a short pre-determined period and permits breeding round the year. The principle of oestrus synchronisation is based on controlling of the luteal phase of the oestrous cycle. There are two basic mechanisms; one by shortening the luteal life (premature luteolysis) using prostaglandins or its analogues and the other by prolonging the luteal life (simulating the activity of natural progesterone produced by the corpus luteum) using exogenous progesterone source. The former is easy to apply and only effective during breeding season, whereas the latter is advantageous when the reproductive status of the goat flock is unknown. The common hormonal products easily available in Nepal includes; prostaglandins or its analogues (Oviprost® Dinoprost® Lutalyse® and Estrumate®), exogenous progesterone (Fluorogestone acetate® and Controlled Internal Drug Release®, CIDR) devices). However, before practicing the oestrous synchronization protocol, it needs to be validated for oestrous response rate, time to onset of oestrous, duration of oestrous and pregnancy rates at farmer’s field. In conclusion, application of oestrus synchronisation practice enhanced goat production and surplus the goat meat demand in Nepal.

Keywords: goat, Nepal, oestrous, synchronization

Procedia PDF Downloads 124

Authors: Pamita Awasthi, Kirna, Shilpa Dogra, Manu Vatsal, Ritu Barthwal

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Doxorubicin, also known as adriamycin, is an anthracycline class of drug used in cancer chemotherapy. It is used in the treatment of non-Hodgkin’s lymphoma, multiple myeloma, acute leukemias, breast cancer, lung cancer, endometrium cancer and ovary cancers. It functions via intercalating DNA and ultimately killing cancer cells. The major side effects of doxorubicin are hair loss, myelosuppression, nausea & vomiting, oesophagitis, diarrhoea, heart damage and liver dysfunction. The minor modifications in the structure of compound exhibit large variation in the biological activity, has prompted us to carry out the synthesis of sulfonamide derivatives. Sulfonamide is an important feature with broad spectrum of biological activity such as antiviral, antifungal, diuretics, anti-inflammatory, antibacterial and anticancer activities. Structure of the synthesized compound N-(1-methyl-2-oxo-2-N-methyl anilino-ethyl)benzene sulfonamide confirmed by proton nuclear magnetic resonance (1H NMR),13C NMR, Mass and FTIR spectroscopic tools to assure the position of all protons and hence stereochemistry of the molecule. Further we have reported the binding potential of synthesized sulfonamide analogues in comparison to doxorubicin drug using Auto Dock 4.2 software. Computational binding energy (B.E.) and inhibitory constant (Ki) has been evaluated for the synthesized compound in comparison of doxorubicin against Poly (dA-dT).Poly (dA-dT) and Poly (dG-dC).Poly (dG-dC) sequences. The in vitro cytotoxic study against human breast cancer cell lines confirms the better anticancer activity of the synthesized compound over currently in use anticancer drug doxorubicin. The IC50 value of the synthesized compound is 7.12 µM where as for doxorubicin is 7.2 µ.

Keywords: Doxorubicin, auto dock, in silco, in vitro

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Authors: Murali Aarthy, Sanjeev Kumar Singh

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High risk human papillomaviruses are highly associated with the carcinoma of the cervix and the other genital tumors. Cervical cancer develops through the multistep process in which increasingly severe premalignant dysplastic lesions called cervical intraepithelial neoplastic progress to invasive cancer. The oncoprotein E7 of human papillomavirus expressed in the lower epithelial layers drives the cells into S-phase creating an environment conducive for viral genome replication and cell proliferation. The replication of the virus occurs in the terminally differentiating epithelium and requires the activation of cellular DNA replication proteins. To date, no suitable drug molecule is available to treat HPV infection whereas identification of potential drug targets and development of novel anti-HPV chemotherapies with unique mode of actions are expected. Hence, our present study aimed to identify the potential inhibitors analogous to EGCG, a green tea molecule which is considered to be safe to use for mammalian systems. A 3D similarity search on the natural small molecule library from natural product database using EGCG identified 11 potential hits based on their similarity score. The structure based docking strategies were implemented in the potential hits and the key interacting residues of protein with compounds were identified through simulation studies and binding free energy calculations. The conformational changes between the apoprotein and the complex were analyzed with the simulation and the results demonstrated that the dynamical and structural effects observed in the protein were induced by the compounds and indicated the dominance to the oncoprotein. Overall, our study provides the basis for the structural insights of the identified potential hits and EGCG and hence, the analogous compounds identified can be potent inhibitors against the HPV 16 E7 oncoprotein.

Keywords: EGCG, oncoprotein, molecular dynamics simulation, analogues

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Authors: Katharigatta N. Venugopala, Fernando Albericio, Bander E. Al-Dhubiab, T. Govender

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Recent years have witnessed a renaissance in the field of peptides that are obtained from various natural sources such as many bacteria, fungi, plants, seaweeds, vertebrates, invertebrates and have been reported for various pharmacological properties such as anti-TB, anticancer, antimalarial, anti-inflammatory, anti-HIV, antibacterial, antifungal, and antidiabetic, activities. In view of the pharmacological significance of natural peptides, serious research efforts of many scientific groups and pharmaceutical companies have consequently focused on them to explore the possibility of developing their potential analogues as therapeutic agents. Solid phase and solution phase peptide synthesis are the two methodologies currently available for the synthesis of natural or synthetic linear or cyclic depsi-peptides. From a synthetic point of view, there is no doubt that the solid-phase methodology gained added advantages over solution phase methodology in terms of simplicity, purity of the compound and the speed with which peptides can be synthesised. In the present study total synthesis, purification and structural elucidation of analogues of natural anti-TB cyclic depsi-peptides such as depsidomycin, massetolides and viscosin has been attempted by solid phase method using standard Fmoc protocols and finally off resin cyclization in solution phase method. In case of depsidomycin, synthesis of linear peptide on solid phase could not be achieved because of two turn inducing amino acids in the peptide sequence, but total synthesis was achieved by convergent solid phase peptide synthesis followed by cyclization in solution phase method. The title compounds obtained were in good yields and characterized by NMR and HRMS. Anti-TB results revealed that the potential title compound exhibited promising activity at 4 µg/mL against H37Rv and 16 µg/mL against MDR strains of tuberculosis.

Keywords: total synthesis, cyclic depsi-peptides, anti-TB activity, tuberculosis

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Authors: Monika Patel, Kazuaki Matsumura

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Synthetic hydrogels, with their unique properties such as porosity, strength, and swelling in aqueous environment, are being used in many fields from food additives to regenerative medicines, from diagnostic and pharmaceuticals to drug delivery systems (DDS). But, hydrogels also have some limitations in terms of homogeneity of drug distribution and quantity of loaded drugs. As an alternate, polymeric micelles are extensively used as DDS. With the ease of self-assembly, and distinct stability they remarkably improve the solubility of hydrophobic drugs. However, presently, combinational therapy is the need of time and so are systems which are capable of releasing more than one drug. And it is one of the major challenges towards DDS to control the release of each drug independently, which simple DDS cannot meet. In this work, we present an amphiphilic polypeptide based micelle hydrogel composite to study the dual drug release for wound healing purposes using Amphotericin B (AmpB) and Curcumin as model drugs. Firstly, two differently charged amphiphilic polypeptide chains were prepared namely, poly L-Lysine-b-poly phenyl alanine (PLL-PPA) and poly Glutamic acid-b-poly phenyl alanine (PGA-PPA) through ring opening polymerization of amino acid N-carboxyanhydride. These polymers readily self-assemble to form micelles with hydrophobic PPA block as core and hydrophilic PLL/PGA as shell with an average diameter of about 280nm. The thus formed micelles were loaded with the model drugs. The PLL-PPA micelle was loaded with curcumin and PGA-PPA was loaded with AmpB by dialysis method. Drug loaded micelles showed a slight increase in the mean diameter and were fairly stable in solution and lyophilized forms. For forming the micelles hydrogel composite, the drug loaded micelles were dissolved and were cross linked using genipin. Genipin uses the free –NH2 groups in the PLL-PPA micelles to form a hydrogel network with free PGA-PPA micelles trapped in between the 3D scaffold formed. Different composites were tested by changing the weight ratios of the both micelles and were seen to alter its resulting surface charge from positive to negative with increase in PGA-PPA ratio. The composites with high surface charge showed a burst release of drug in initial phase, were as the composites with relatively low net charge showed a sustained release. Thus the resultant surface charge of the composite can be tuned to tune its drug release profile. Also, while studying the degree of cross linking among the PLL-PPA particles for effect on dual drug release, it was seen that as the degree of crosslinking increases, an increase in the tendency to burst release the drug (AmpB) is seen in PGA-PPA particle, were as on the contrary the PLL-PPA particles showed a slower release of Curcumin with increasing the cross linking density. Thus, two different pharmacokinetic profile of drugs were seen by changing the cross linking degree. In conclusion, a unique charged amphiphilic polypeptide based micelle hydrogel composite for dual drug delivery. This composite can be finely tuned on the basis of need of drug release profiles by changing simple parameters such as composition, cross linking and pH.

Keywords: amphiphilic polypeptide, dual drug release, micelle hydrogel composite, tunable DDS

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Authors: Abhay Asthana, Shally Toshkhani, Gyati Shilakari

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The objective of the present research work is to develop a topical biodegradable dermal patch based formulation to aid accelerated wound healing. It is always better for patient compliance to be able to reduce the frequency of dressings with improved drug delivery and overall therapeutic efficacy. In present study optimized formulation using biodegradable components was obtained evaluating polymers and excipients (HPMC K4M, Ethylcellulose, Povidone, Polyethylene glycol and Gelatin) to impart significant folding endurance, elasticity, and strength. Molten gelatin was used to get a mixture using ethylene glycol. Chitosan dissolved in acidic medium was mixed with stirring to Gelatin mixture. With continued stirring to the mixture Curcumin was added with the aid of DCM and Methanol in an optimized ratio of 60:40 to get homogenous dispersion. Polymers were dispersed with stirring in the final formulation. The mixture was sonicated casted to get the film form. All steps were carried out under strict aseptic conditions. The final formulation was a thin uniformly smooth textured film with dark brown-yellow color. The film was found to have folding endurance was around 20 to 21 times without a crack in an optimized formulation at RT (23°C). The drug content was in range 96 to 102% and it passed the content uniform test. The final moisture content of the optimized formulation film was NMT 9.0%. The films passed stability study conducted at refrigerated conditions (4±0.2°C) and at room temperature (23 ± 2°C) for 30 days. Further, the drug content and texture remained undisturbed with stability study conducted at RT 23±2°C for 45 and 90 days. Percentage cumulative drug release was found to be 80% in 12h and matched the biodegradation rate as tested in vivo with correlation factor R2>0.9. In in vivo study administration of one dose in equivalent quantity per 2 days was applied topically. The data demonstrated a significant improvement with percentage wound contraction in contrast to control and plain drug respectively in given period. The film based formulation developed shows promising results in terms of stability and in vivo performance.

Keywords: wound healing, biodegradable, polymers, patch

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Authors: Abhay Asthana, Gyati Shilakari Asthana

Abstract:

It’s the patient compliance and stability in combination with controlled drug delivery and biocompatibility that forms the core feature in present research and development of sustained biodegradable patch formulation intended for wound healing. The aim was to impart sustained degradation, sterile formulation, significant folding endurance, elasticity, biodegradability, bio-acceptability and strength. The optimized formulation was developed using component including polymers including Hydroxypropyl methyl cellulose, Ethylcellulose, and Gelatin, and Citric Acid PEG Citric acid (CPEGC) triblock dendrimers and active Curcumin. Polymeric mixture dissolved in geometric order in suitable medium through continuous stirring under ambient conditions. With continued stirring Curcumin was added with aid of DCM and Methanol in optimized ratio to get homogenous dispersion. The dispersion was sonicated with optimum frequency and for given time and later casted to form a patch form. All steps were carried out under under strict aseptic conditions. The formulations obtained in the acceptable working range were decided based on thickness, uniformity of drug content, smooth texture and flexibility and brittleness. The patch kept on stability using butter paper in sterile pack displayed folding endurance in range of 20 to 23 times without any evidence of crack in an optimized formulation at room temperature (RT) (24 ± 2°C). The patch displayed acceptable parameters after stability study conducted in refrigerated conditions (8±0.2°C) and at RT (24 ± 2°C) upto 90 days. Further, no significant changes were observed in critical parameters such as elasticity, biodegradability, drug release and drug content during stability study conducted at RT 24±2°C for 45 and 90 days. The drug content was in range 95 to 102%, moisture content didn’t exceeded 19.2% and patch passed the content uniformity test. Percentage cumulative drug release was found to be 80% in 12h and matched the biodegradation rate as drug release with correlation factor R2>0.9. The biodegradable patch based formulation developed shows promising results in terms of stability and release profiles.

Keywords: sustained biodegradation, wound healing, polymers, stability

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Authors: Menna Ewida, Dalal Abou El-Ella, Dina Lasheen, Huessin El-Subbagh

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Introduction: Vascular Endothelial Growth Factor receptor (VEGF) is a signal protein produced by cells that stimulates vasculogenesis to create new blood vessels. VEGF family binds to three trans-membrane tyrosine kinase receptors,Dihydrofolate reductase (DHFR) is an enzyme of crucial importance in medicinal chemistry. DHFR catalyzes the reduction 7,8 dihydro-folate to tetrahydrofolate and intimately couples with thymidylate synthase which is a pivotal enzyme that catalysis the reductive methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) utilizing N5,N10-methylene tetrahydrofolate as a cofactor which functions as the source of the methyl group. Purpose: Novel substituted Thiazole agents were designed as DHFR and VEGF-TK inhibitors with increased synergistic activity and decreased side effects. Methods: Five series of compounds were designed with a rational that mimic the pharmacophoric features present in the reported active compounds that target DHFR & VEGFR. These molecules were docked against Methotrexate & Sorafenib as controls. An in silico ADMET study was also performed to validate the bioavailability of the newly designed compounds. The in silico molecular docking & ADMET study were also applied to the non-classical antifolates for comparison. The interaction energy comparable to that of MTX for DHFRI and Sorafenib for VEGF-TKI activity were recorded. Results: Compound 5 exhibited the highest interaction energy when docked against Sorafenib, While Compound 9 showed the highest interaction energy when docked against MTX with the perfect binding mode. Comparable results were also obtained for the ADMET study. Most of the compounds showed absorption within (95-99) zone which varies according to the type of substituents. Conclusions: The Substituted Thiazole Analogues could be a suitable template for antitumor drugs that possess enhanced bioavailability and act as DHFR and VEGF-TK inhibitors.

Keywords: anti-tumor agents, DHFR, drug design, molecular modeling, VEGFR-TKIs

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Authors: Asha Gupta, Ramandeep Kaur

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The purpose of this paper is to study a class of closed sets, called generalized pre-closed sets with respect to an ideal (briefly Igp-closed sets), which is an extension of generalized pre-closed sets in general topology. Then, by using these sets, the concepts of Igp- compact spaces along with some classes of maps like continuous and closed maps via ideals have been introduced and analogues of some known results for compact spaces, continuous maps and closed maps in general topology have been obtained.

Keywords: ideal, gp-closed sets, gp-closed maps, gp-continuous maps

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Authors: Adriana Muñoz-Talavera, Ana Rosa Rincón-Sánchez, Abraham Escobedo-Moratilla, María Cristina Islas-Carbajal, Miguel Ángel Gómez-Lim

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The highest rates of diabetes incidence and prevalence worldwide will increase the number of diabetic patients requiring insulin or insulin analogues. Then, current production systems would not be sufficient to meet the future market demands. Therefore, developing efficient expression systems for insulin and insulin analogues are needed. In addition, insulin analogues with better pharmacokinetics and pharmacodynamics properties and without mitogenic potential will be required. SCI-57 (single chain insulin-57) is an insulin analogue having 10 times greater affinity to the insulin receptor, higher resistance to thermal degradation than insulin, native mitogenicity and biological effect. Plants as expression platforms have been used to produce recombinant proteins because of their advantages such as cost-effectiveness, posttranslational modifications, absence of human pathogens and high quality. Immunoglobulin production with a yield of 50% has been achieved by transient expression in Nicotiana benthamiana (Nb). The aim of this study is to produce SCI-57 by transient expression in Nb. Methodology: DNA sequence encoding SCI-57 was cloned in pICH31070. This construction was introduced into Agrobacterium tumefaciens by electroporation. The resulting strain was used to infiltrate leaves of Nb. In order to isolate SCI-57, leaves from transformed plants were incubated 3 hours with the extraction buffer therefore filtrated to remove solid material. The resultant protein solution was subjected to anion exchange chromatography on an FPLC system and ultrafiltration to purify SCI-57. Detection of SCI-57 was made by electrophoresis pattern (SDS-PAGE). Protein band was digested with trypsin and the peptides were analyzed by Liquid chromatography tandem-mass spectrometry (LC-MS/MS). A purified protein sample (20µM) was analyzed by ESI-Q-TOF-MS to obtain the ionization pattern and the exact molecular weight determination. Chromatography pattern and impurities detection were performed using RP-HPLC using recombinant insulin as standard. The identity of the SCI-57 was confirmed by anti-insulin ELISA. The total soluble protein concentration was quantified by Bradford assay. Results: The expression cassette was verified by restriction mapping (5393 bp fragment). The SDS-PAGE of crude leaf extract (CLE) of transformed plants, revealed a protein of about 6.4 kDa, non-present in CLE of untransformed plants. The LC-MS/MS results displayed one peptide with a high score that matches SCI-57 amino acid sequence in the sample, confirming the identity of SCI-57. From the purified SCI-57 sample (PSCI-57) the most intense charge state was 1069 m/z (+6) on the displayed ionization pattern corresponding to the molecular weight of SCI-57 (6412.6554 Da). The RP-HPLC of the PSCI-57 shows the presence of a peak with similar retention time (rt) and UV spectroscopic profile to the insulin standard (SCI-57 rt=12.96 and insulin rt=12.70 min). The collected SCI-57 peak had ELISA signal. The total protein amount in CLE from transformed plants was higher compared to untransformed plants. Conclusions: Our results suggest the feasibility to produce insulin analogue SCI-57 by transient expression in Nicotiana benthamiana. Further work is being undertaken to evaluate the biological activity by glucose uptake by insulin-sensitive and insulin-resistant murine and human cultured adipocytes.

Keywords: insulin analogue, mass spectrometry, Nicotiana benthamiana, transient expression

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Authors: J. O. Ezekwesili-Ofili, L. I. Okorafor, S. C. Nsofor

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Diabetes mellitus is a carbohydrate metabolism disorder due to an absolute or relative deficiency of insulin secretion, action or both. Many known hypoglycaemic drugs are known to produce serious side effects. However, the search for safer and more effective agents has shifted to plant products, including foods and spices. One of such is the rhizome of Curcuma longa or turmeric, which is a spice with high medicinal value. A drawback in the use of C. longa is the poor bioavailability of curcumin, the active ingredient. It has been reported that piperine, an alkaloid present in peppers increases the bioavailability of curcumin. This work therefore investigated the hypoglycaemic and antioxidant effects of ethanolic extract of C. longa rhizomes, alone and with two pepper adjuvants in alloxan-induced diabetic rats. A total of 48 rats were divided into 6 groups of 8 rats each. Groups A–E were induced with diabetes using 150mg/kg body weight of alloxan monohydrate, while group F was normoglycaemic: Group A: Diabetic; fed with 400 mg/g body weight of turmeric extract; group B: Diabetic, fed with 400 mg/kg b. w. and 200mg/kg b. w of ethanolic extract of seeds of Piper guinensee; group C: Diabetic, fed with 400 mg/kg b. w. and 200 mg /kg b. w. of ethanolic extract of seeds of Capsicum annum var cameroun, group D: Diabetic, treated with standard drug, glibenclamide (0.3mg/kg body weight), group E: Diabetic; no treatment i.e. Positive control and group F: non diabetic, no treatment i.e. Negative control. Blood glucose levels were monitored for 14 days using a glucometer. The levels of the antioxidant enzymes; glutathione peroxidase, catalase and superoxide dismutase were also assayed in serum. The ethanolic extracts of C. longa rhizomes at the dose given (400 mg/kg b. w) significantly reduced the blood glucose levels of the diabetic rats (p<0.05) comparable to the standard drug. Co administration of extract of the peppers did not significantly increase the efficiency of the extract, although C. annum var cameroun showed greater effect, though not significantly. The antioxidant effect of the extract was significant in diabetic rats. The use of piperine-containing peppers enhanced the antioxidant effect. Phytochemical analyses of the ethanolic extract of C. longa showed the presence of alkaloids, flavonoids, steroids, saponins, tannins, glycosides, and terpenoids. These results suggest that the ethanolic extract of C. longa had antidiabetic with antioxidant effects and could thus be of benefit in the treatment and management of diabetes as well as ameliorate pro-oxidant effects that may lead to diabetic complications. However, while the addition of piperine did not affect the antidiabetic effect of C. longa, the antioxidant effect was greatly enhanced.

Keywords: antioxidant, Curcuma longa rhizome, hypoglycaemic, pepper adjuvants, piperine

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Authors: H. Yousefnia, MS. Mousavi-Daramoroudi, S. Zolghadri, F. Abbasi-Davani

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High expression of somatostatin receptors on a wide range of human tumours makes them as potential targets for peptide receptor radionuclide tomography. A series of octreotide analogues were synthesized while [DOTA-DPhe1, Tyr3]octreotide (DOTATOC) indicated advantageous properties in tumour models. In this study, 177Lu-DOTATOC was prepared with the radiochemical purity of higher than 99% in 30 min at the optimized condition. Biological behavior of the complex was studied after intravenous injection into the Syrian rats. Major difference uptake was observed compared to 177LuCl3 solution especially in somatostatin receptor-positive tissues such as pancreas and adrenal.

Keywords: Biodistribution, 177Lu, Octreotide, Syrian rats

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Authors: Shradha S. Binani, Pravin S. Bodke, Ravi V. Joat

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An efficient method has been described for the synthesis of 6-(substituted aryl)-4-(2'- hydroxy-5'-chlorophenyl)-1, 6-dihydropyrimidine-2-thiol, as a beneficial antibacterial and antifungal agents. The diketones of title compounds were synthesized in four steps and subsequently these diketones were further reacted with thiourea in the presence of DMF, which led to the formation of dihydropyrimidine derivatives 5 (a-f). Compounds 5 (a-f) were screened for their in vitro antibacterial and antifungal activity by agar well method. Compounds 5b, 5c, 5e, and 5f were exhibited significant antimicrobial potential against tested strains at 50ug/ml and 100ug/ml concentrations. Six novel dihydropyrimidine analogues have been synthesized, characterized and found to be promising antibacterial and antifungal agents.

Keywords: diketones, dihyropyrimidine, antimicrobial activity, thiol group

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Authors: U. Arjun, K. Brinda, M. Padmanabhan, R. Nath

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Polycrystalline samples of rare-earth oxy-carbonates Ln2O2CO3 (Ln = Nd, Sm, and Dy) are synthesized, and their structural and magnetic properties are investigated. All of them crystallize in a hexagonal structure with space group P6_3/mmc. They form a double layered structure with frustrated triangular arrangement of rare-earth magnetic ions. An antiferromagnetic transition is observed at TN ≈ 1.25 K, 0.61 K, and 1.21 K for Nd2O2CO3, Sm2O2CO3, and Dy2O2CO3, respectively. From the analysis of magnetic susceptibility, the value of the Curie-Weiss temperature θ_CW is obtained to be ≈ 21.7 K, 18 K, and 10.6 K for Nd2O2CO3, Sm2O2CO3, and Dy2O2CO3, respectively. The magnetic frustration parameter f ( = |θ_CW|/T_N) is calculated to be ≈ 17.4, 31, and 8.8 for Nd2O2CO3, Sm2O2CO3, and Dy2O2CO3, respectively which indicates that Sm2O2CO3 is strongly frustrated compared to its Nd and Dy analogues.

Keywords: chemical synthesis, exchange and superexchange, heat capacity, magnetically ordered materials

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Authors: Farah Marsusi, Mohammad Qasemnazhand

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Density-functional theory (DFT) was applied to investigate the geometry and electronic properties H-terminated Si-fullerene (Si-fullerane). Natural bond orbital (NBO) analysis confirms sp3 hybridization nature of Si-Si bonds in Si-fulleranes. Quantum confinement effect (QCE) does not affect band gap (BG) so strongly in the size between 1 to 1.7 nm. In contrast, the geometry and symmetry of the cage have significant influence on BG. In contrast to their carbon analogues, pentagon rings increase the stability of the cages. Functionalized Si-cages are stable and can be chemically very active. The electronic properties are highly sensitive to the surface chemistry via functionalization with different chemical groups. As a result, BGs and chemical activities of these cages can be drastically tuned through the chemistry of the surface.

Keywords: density functional theory, sila-fullerens, NBO analysis, opto-electronic properties

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Authors: Hassina Harkat, Samiha Taybe, Salima Loucif, Valérie Beneteau, Patrick Pale

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Indole and its derivatives have attracted great interest because of their importance in the synthetic organic and medicinal chemistry. They are widely used as anti hypertension, anti tubercular, anticancer activity, antiviral, Alzheimer's disease, antioxidant properties, and free radical induced lipid peroxidation. Many drugs and natural products contain indole moiety, such as the vinca alkaloids, fungal metabolites and marine natural products. Generally applicable synthetic methods for indole moiety involve ring closure to form the pyrrole. Indole derivatives can also be accessed by further functionalization of the indole nucleus. Therefore we report a mild and efficient protocol for the synthesis of analogues of indole catalyzed via zeolithe USY doped with CuI under solvent-free conditions.

Keywords: indole, zeolithe, USY-CuI, heterogeneous catalysis

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Authors: S. Jayasinghe, W. G. D. Wickramasingha, V. Karunaratne, D. N. Karunaratne, A. Ekanayake

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Multi-drug resistant microbial pathogens are a serious global health problem, and hence, there is an urgent necessity for discovering new drug therapeutics. However, finding alternatives is a one of the biggest challenges faced by the global drug industry due to the spiraling high cost and serious side effects associated with modern medicine. On the other hand, plants and their secondary metabolites can be considered as good sources of scaffolds to provide structurally diverse bioactive compounds as potential therapeutic agents. 6β-hydroxy betunolic acid is a triterpenoid isolated from bark of Schumacheria castaneifolia which is an endemic plant to Sri Lanka which has shown antibacterial activity against both Staphylococcus aureus (ATCC 29213) and methicillin-resistant S. aureus with Minimum Inhibition Concentration (MIC) of 16 µg/ml. The objective of this study was to determine the anti-bacterial activity for the derivatives of 6β- hydroxy betunolic acid against standard strains of Staphylococcus aureus (ATCC 29213 and ATCC 25923), Enterococcus faecalis (ATCC 29212), Escherichia coli (ATCC 35218 and ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), carbepenemas produce Kebsiella pneumonia (ATCC BAA 1705) and carbepenemas non produce Kebsiella pneumonia (ATCC BAA 1706) and four stains of clinically isolated methicillin resistance S. aureus and Acinetobacter. Structural analogues of 6β-hydroxy betunolic acid were synthesized by modifying the carbonyl group at C-3 to obtain olefin and oxime, the hydroxyl group at C-6 position to a ketone, the carboxylic acid at C-17 to obtain amide and halo ester and the olefin group at C-20 position to obtain epoxide. Chemical structures of the synthesized analogues were confirmed with spectroscopic data and antibacterial activity was determined through broth micro dilution assay. Results revealed that 6β- hydroxy betunolic acid shows significant antibacterial activity only against the Gram positive strains and it was inactive against all the tested Gram negative strains for the tested concentration range. However, structural modifications into oxime and olefin at C-3, ketone at C-6 and epoxide at C-20 decreased its antibacterial activity against the gram positive organisms and it was totally lost with the both modifications at C-17 into amide and ester. These results concluded that the antibacterial activity of 6β- hydroxy betunolic acid and derivatives is predominantly depending on the cell wall difference of the bacteria and the presence of carboxylic acid at C-17 is highly important for the antibacterial activity against Gram positive organisms.

Keywords: antibacterial activity, 6β- hydroxy betunolic acid, broth micro dilution assay, structure activity relationship

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