ANTIPROLIFERATIVE AND DNA CLEAVAGE ACTIVITY OF VARIOUS SOLVENT EXTRACTS OF ACACIA FARNESIANA LINN. POD

Objective: Cancer has become the major disease by uncontrolled cell growth effecting large population on the globe. This study, deals with antiproliferative activity of different solvent extracts, viz., n-hexane (S1), dichloromethane (DCM) (S2), and methanol (S3) of Acacia farnesiana pod on four cancer cell lines, viz., chronic myelogenous leukemia (K562), breast cancer (MCF-7), hepatocellular carcinoma (HePG2), colorectal adenocarcinoma (Colo 205), and DNA cleavage activity of the extracts on CT-DNA.Methods: The antiproliferative study was performed by MTT assay and DNA cleavage studies of the solvent extracts (S1, S2, and S3) and its fractions (S4 and S5) was carried out by agarose gel electrophoresis method.Results: The antiproliferative activity results revealed that n-hexane extract (S1) has showed activity against MCF-7 (21.70 %) cell line and methanol extract (S3) against K562 (24.5%) and HePG2 (23.3%) cell lines. The DNA cleavage could be seen at every concentration tested by n-hexane (S1), DCM (S2), and methanol (S3) extracts and significant cleavage was observed at concentrations of 25, 50, and 100 μg by fractions (S4) and (S5) of methanol extract.Conclusion: The results indicated that the extract of A. farnesiana pod (n-hexane and methanol) has antiproliferative properties and the DNA cleavage studies performed on CT-DNA was found that the extracts and its fractions showed significant activity at the concentrations tested

ANTIMICROBIAL AND IN SILICO ADMET SCREENING OF NOVEL (E)-N-(2-(1H-INDOL-3-YL-AMINO) VINYL)-3-(1-METHYL-1H-INDOL-3-YL)-3-PHENYLPROPANAMIDE DERIVATIVES

Objective: Synthesis, in silico absorption, distribution, metabolism, excretion, toxicity (ADMET) and in vitro antimicrobial screening of (E)-N-(2-(1H-indol-3-ylamino) vinyl)-3-(1-methyl-1H-indol-3-yl)-3-phenylpropanamide derivatives.Methods: (E)-N-(2-(1H-indol-3-ylamino) vinyl)-3-(1-methyl-1H-indol-3-yl)-3 phenylpropane-amide derivatives were synthesized by combining indole ethanolamine and substituted Meldrum's adduct. The synthesized compounds were subjected to in vitro antimicrobial study by cup plate method and in silico ADMET properties using ACD/I-Lab 2.0.Results: The in vitro antimicrobial screening against precarious pathogenic microorganisms viz, Pseudomonas aureginosa, Staphylococcus aureus, Escherichia coli, Vibrio cholerae, and the antifungal activity against Candida albicans, Aspergillus niger, Penicillin chrysogenum and Cladosporium oxysporum strains. The results revealed that compounds 5b, 5c, 5d and 5e showed good antimicrobial property and obeyed the in silico pharmacokinetic parameters.Conclusion: The encouraging results exhibited by the compounds (E)-N-(2-(1H-indol-3-ylamino) vinyl)-3-(1-methyl-1H-indol-3-yl)-3-phenyl propanamide derivatives, 5(a-e) can be explored as possible hits in antimicrobial therapy. The molecules obey the Lipinski rule of five when tested in silico and can be used in understanding the quantitative structure-activity relationship (QSAR) parameters

Ethyl 4-(4′-heptanoyloxyphenyl)-6-methyl-3,4-dihydropyrimidin-2-one-5-carboxylate Prevents Progression of Monocrotaline-induced Pulmonary Arterial Hypertension in Rats

Therapies to prevent onset and progression of pulmonary arterial pressure are not very effective yet. This study was designed to investigate the effects of a novel dihydropyrimidinone, ethyl 4-(4′-heptanoyloxyphenyl)-6-methyl-3,4-dihydropyrimidin-2-one-5-carboxylate (H-DHPM) on pathogenesis of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). For the same purpose, rats were injected intraperitoneally (i.p.) a single dose (60 mg/kg) of MCT which led to development of PAH in 21 days. MCT insult caused high mortality, pulmonary vascular and parenchymal remodelling. Since the course of PAH pathogenesis is characterised by an early onset and progression phases, H-DHPM was administered i.p. at 30 mg/kg dosage in MCT pre-injected animals either from day 0 through day 21 or day 14 though day 21 of MCT injection in two separate treatment groups. H-DHPM significantly improved survival, prevented remodelling of pulmonary vasculature and parenchyma and subsequently ameliorated PAH pathogenesis. Moreover, we observed significant decrease in right ventricle hypertrophy, measured by wet weight of right ventricle (RV) divided by wet weight of left ventricle plus septum (LV+S), in H-DHPM treated groups as compared to MCT injected animals. These findings suggest H-DHPM not only prevented development of PAH but also treated the PAH pathogenesis in progressive phase. In conclusion, our data determines H-DHPM, might be a future drug for the prevention of PAH

ANTIPROLIFERATIVE, ADME AND POTENTIAL IN SILICO G6PDH INHIBITORY ACTIVITY OF NOVEL 2-(1-BENZOFURAN-2-YL)-4-(5-PHENYL-4H-1, 2, 4-TRIAZOL-3-YL) QUINOLINE DERIVATIVES

Objectives: Synthesis of new 2-(1-benzofuran-2-yl)-4-(5-phenyl-4H-1, 2, 4-triazol-3-yl) quinoline and its derivatives for antiproliferative potential against cancer cells.Methods: The general methods were employed for the synthesis and the structures were confirmed by IR, 1H-NMR, 13C-NMR and mass spectral analysis. The antiproliferative activity was performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and molecular docking study were performed by Auto Dock Tools. In silico Absorption-Distribution-Metabolism-Excretion-Toxicity (ADMET) study for the drug, likeliness was carried out on ACD/lab-2.Results: The compound 3l showed 44, 44, 38 and 37 % inhibition against MCF-7, HepG2, Colo205 and HeLa cell lines, respectively; whereas, the compounds 3i and 3j exhibited 49 and 42 % inhibition against MCF-7 cell line. The molecular docking study revealed that the compound 3i has the lowest binding energy (-8.60 Kcal mol-1), suggesting to be potentially best inhibitor of Glucose-6-phosphate dehydrogenase (G6PDH). The in silico ADME analysis also revealed that compound 3i does not violate any of the Lipinski rules of five and has the best stimulative human colonic absorption up to 95 %.Conclusion: The study reveals that the compounds containing benzofuran coupled nitrogen heterocycles are essential for activity as they possess excellent drug-like characteristics.Â

Ibuprofen Loaded Electrospun Polymeric Nanofibers: A Strategy to Improve Oral Absorption

The poor aqueous solubility of candidate drugs has presented a great challenge to formulation scientists for their effective oral delivery. Poor solubility is often associated with poor dissolution behavior and, subsequently, poor bioavailability for those drugs when intestinal absorption is dissolution rate limited. In the present study electrospun polymeric nanofibers were developed to address the poor aqueous solubility of ibuprofen, a Biopharmaceutic Classification System (BCS) class-II drug. Hydrophilic spinnable polymers like polyvinyl pyrrolidone were deployed as a carrier system for the fabrication of nanofibers. The electrospinning parameters like flow rate, voltage, and spinneret to collector distance were optimized. The fabricated ibuprofen-loaded nanofibers were characterized using scanning electron microscopy and differential scanning calorimetry. Drug release studies and ex vivo intestinal absorption studies were also carried out. The nanofiber-based platform significantly improved in vitro absorption of ibuprofen compared to pure ibuprofen crystals

Size-controlled synthesis of monodispersed gold nanoparticles via carbon monoxide gas reduction

An in depth analysis of gold nanoparticle (AuNP) synthesis and size tuning, utilizing carbon monoxide (CO) gas as a reducing agent, is presented for the first time. The sizes of the AuNPs are tunable from ~4 to 100 nm by altering the concentration of HAuCl4 and inlet CO gas-injection flow rate. It is also found that speciation of aqueous HAuCl4, prior to reduction, influences the size, morphology, and properties of AuNPs when reduced with CO gas. Ensemble extinction spectra and TEM images provide clear evidence that CO reduction offers a high level of monodispersity with standard deviations as low as 3%. Upon synthesis, no excess reducing agent remains in solution eliminating the need for purification. The time necessary to synthesize AuNPs, using CO, is less than 2 min

Gauge coupling unification with large extra dimensions

We make a detailed study of the unification of gauge couplings in the MSSM with large extra dimensions. We find some scenarios where unification can be achieved (with the strong coupling constant at the Z mass within one standard deviation of the experimental value) with both the compactification scale and the SUSY breaking scale in the few TeV range. No enlargement of the gauge group or particle content is needed. One particularly interesting scenario is when the SUSY breaking scale is larger than the compactification scale, but both are small enough to be probed at the CERN LHC. Unification in two scales scenarios is also investigated and found to give results within the LHC.Comment: 17 pages, 3 figures, some discussions added, few additional references included. Version to appear in Phys. Rev.

District level baseline survey of family planning program in Uttar Pradesh: Pithoragarh

In 1992, the Ministry of Health and Family Welfare and the United States Agency for International Development, New Delhi, began the Innovations in Family Planning Services Project (IFPS) under the management of the State Innovation in Family Planning Services Agency (SIFPSA), Lucknow. The goal was to reduce the fertility rate in Uttar Pradesh by expanding and improving family planning (FP) services. To achieve this, the IFPS project will support service innovations in the public sector and nongovernmental sectors and through contraceptive social marketing mechanisms. The Baseline Survey in Uttar Pradesh (BSUP) is being undertaken as one important component of the IFPS project. The BSUP is designed to provide information on fertility, FP, and maternal and child health care that will be helpful in monitoring and evaluating population and family welfare policies and programs. SIFPSA has designated the Population Council as the nodal organization responsible for providing technical guidance for the survey. The responsibility of conducting this multicentric survey in the district of Pithoragarh was given to the Indian Institute of Health Management Research, Jaipur

District level baseline survey of family planning program in Uttar Pradesh: Nainital

In 1992, the Ministry of Health and Family Welfare and the United States Agency for International Development, New Delhi, began the Innovations in Family Planning Services Project (IFPS) under the management of the State Innovation in Family Planning Services Agency (SIFPSA), Lucknow. The goal was to reduce the fertility rate in Uttar Pradesh by expanding and improving family planning (FP) services. To achieve this, the IFPS project will support service innovations in the public and nongovernmental sectors and through contraceptive social marketing mechanisms. The Baseline Survey in Uttar Pradesh (BSUP) is being undertaken as one important component of the IFPS project. The BSUP is designed to provide information on fertility, FP, and maternal and child health care that will be helpful in monitoring and evaluating population and family welfare policies and programs. SIFPSA has designated the Population Council as the nodal organization responsible for providing technical guidance for the survey. The Indian Institute of Health Management Research, Jaipur, will conduct the survey in the district of Nainital

Facile ZnO NPs catalyzed synthesis of substituted 4-amino-6-(1H-benzimidazol-2-ylsulfanyl)benzene-1,3-dicarbonitrile new derivatives as Potent biological agents

This study focuses on the efficient synthesis of series of substituted 4-amino-6-(1H-benzimidazol-2-ylsulfanyl) benzene-1,3-dicarbonitrile derivatives synthesized from aldehydes, propanedinitrile, substituted thiols and catalyzed by ZnO nanoparticles (ZnONPs). All the synthesized compounds have been characterized using different spectroscopic techniques such as FT-IR, 1H-NMR, C13-NMR and Mass. The compounds were evaluated for potential pharmacological applications, including antimicrobial, α-amylase inhibitory and anticancer activities. Computational calculations, DFT, in-silico molecular docking, and ADME-toxicologystudies were performed. ADMET studies indicated that all synthesized compounds adhered to Rule of five with good bioavailability. This research underscores the promising pharmacological prospects of the synthesized newbenzimidazole derivatives