Sanjay Jain

Insights through AM1 calculations into the structural requirement of 3,4,6-substituted-2-quinolone analogs towards FMS kinase inhibitory activity.

In the present work, we focused on quantification of activity of 3,4,6-substituted-2-quinolone derivatives with reference to structural properties. The multi-variant regression expressions were developed through sequential multiple linear regression technique, considering adjustable correlation coefficient (r(adj)(2)). The amalgamated best fit consensus scoring function showed coefficient of determination (0.891), leave one out cross validated squared correlation coefficient (0.776) and external predictivity value (0.668). The detailed structural investigation revealed that the FMS kinase inhibitory activity is predominantly explained by the topological descriptor, functional group, RDF and MoRSE code. The structural insights gleaned from the study could be usefully employed to design inhibitors with a much more enhanced potency.

Computational evaluation of 2-amino-5-sulphonamido-1,3,4-thiadiazoles as human carbonic anhydrase-IX inhibitors: an insight into the structural requirement for the anticancer activity against HEK 293

Carbonic anhydrase inhibitors are very interesting target for designing anticancer agents. A computational procedure was performed on some thiadiazoles derived from carbonic anhydrase inhibitor acetazolamide. Two important procedures in computational drug discovery, namely docking for modeling ligand–receptor interactions and quantitative structure–activity relationships were employed. The relationship between cytotoxic activity and various descriptors was established by stepwise multiple regression analysis. The analyses have produced well predictive and statistically significant quantitative structure–activity relationships models, which were further cross validated. Among several models, one model has good statistical significance (r = 0.89, Ftest = 6.88, S = 0.33, chance correlation < 0.01), indicates that steric descriptors like EleE are contributing positively to the biological activity, electronic descriptors like connolly molecular surface area and Chi descriptors like chi0 and information theory index like IdAvg are contributing negatively to the biological activity and play a significant role in receptor binding which helps to design some expectedly potent compounds. In order to confirm the obtained results through this ligand-based method, docking was performed on the selected compounds by the use of Schrödinger GLIDE program. Incorporating available biochemical and computational data to the model by correcting the conformation of a single residue lining the binding pocket resulted in significantly improved docking poses. The molecular modeling study allowed confirming the preferential binding mode of reported compounds inside the active site.

FORMULATION AND CHARACTERIZATION OF ALLICIN-AMPHOTERICIN-B LIPOSOMAL GEL FOR THE TREATMENT OF FUNGAL INFECTIONS

Spherical multilammelar vesicles of liposome consisting of lipid egg phosphatidylcholine, soya lecithin and cholesterol were prepared by thin film hydration technique. Further liposomal gel was prepared by egg phosphatidylcholine and cholesterol of molar ratio 7:3 and attained slow drug release with Allicin- Amphotericin B liposomal based gels as compared to the plane gel. Liposomal gel was characterized for drug release kinetics, antifungal activity (disc diffusion assay). Formulation F8 A shows highest drug release. Allicin (Allium sativum Linn.) showed a minimum inhibitory concentration (MIC) at the dose range from 0.195 µg/ml to 10 µg/ml of broth against all fungal strains (F2B Formulation). These lower concentrations were achievable for fungistatic effect and the reduced adverse effects. The results suggest that liposomal gel of Amphotericin B may be useful in the treatment of Topical Fungal Infections.

Pharmacological investigation of leaves of Polypodium decumanum for anti-bacterial activity against gram-positive and gram-negative bacteria

http://dx.doi.org/10.21276/IJRDPL.227 8-0238.2017.6(4).2685-2688 ABSTRACT:The widespread use of antibiotics has led to an increase in multidrugresistant bacteria, which represent a serious risk of infection, in view of this problem the aim of this research was performed to characterize the antibacterial effect of ethanolic and petroleum ether extract of Polypodium decumanum leaves against three gram-positive bacteria(Staphylococcus aureus, Bacillus subtilius, and Streptococcus pyogenes) and three gram-negative bacteria(Pseudomonas aeruginosa, Escherichia coli, and Pseudomonas alcaligenes) in vitro by disc-diffusion method. In this study, we have taken 3 concentrations of Polypodium decumanumplant extract (ethanolic and petroleum ether) viz. 50 mg/ml, 100 mg/ml, and 200 mg/ml, and observed that the ethanolic extract of Polypodium decumanumof the concentration of 200 mg/ml showed higher antibacterial effect compare to other concentration against all 3 gram-positive bacteria and all 3 gram-negative bacteria, but not higher than standard drug Ampicillin.

Production of Rifamycin using Nocardia mediterranea (ATCC 13865)

http://dx.doi.org/10.21276/IJRDPL.227 8-0238.2017.6(4). 2693-2696 ABSTRACT: The U.V. irradiation to Nocardia mediterranea ATCC 13865 for 10, 20, 30, 40, 50, 60, 70, up to 120 minute the maximum (581μgml) production of rifamycin was found developed S-10 strain for maximum production of rifamycin antibiotics (optimum time 15 minute) for further enhancement of rifamycin various parameter like age and size inoculum, pH of the culture medium, various carbohydrate, various amino acids, temperature, various Carbone sources, aeration were optimized. The maximum rifamycin conc. of 570 μgml at 4.50 inoculums % with the age of 48 hrs. Inoculum was given even maximum rifamycin production with various age of inoculums (24, 36, 48, 60, 72 hrs.) with corresponding inoculums % (1.5, 2.5, 3.5, 4.5) in culture media, the optimum rifamycin 485 and 480 μgml of rifamycin was producing M-6 and M-8 respectively medium amongst M-1, 2, 3, 4, 5, 6, 7, 8, 9 and M-10.

Development of Proniosomal Gel: in-vitro, ex-vivo and in-vivo Characterization

The aim of the present research work was to characterize the ex-vivo, in-vitro and in-vivo studies of proniosomal (PN) gel of ketorolac tromethamine (KT). Experimental work: Proniosomal suspension was prepared by rotatory flask evaporator with addition of nonionic surfactant (Sodium Cholate) at concentration ranges (3%, 2% and 1%). Co-solvent like isopropanol, butanol and ethanol as well as dimethyl sulphoxide (DMSO), was later added which act as permeability enhancers in gel formulations. Carbopol 940 was added as the gelling agent in proniosomal suspension. Characterization: PN gel acts as percutaneous enhancers on the transdermal permeability hence were investigated for ex-vivo (Franz Diffusion Cell), in-vitro (Membrane Diffusion Technique) and in-vivo (Estimation of KT in serum at different time intervals by RP-HPLC) studies. Effect of KT on acute inflammation was evaluated in rat carrageenan-induced edema model. Results: Proniosomal gel formulation F1 consisting of sodium cholate, isopropanol and soya lecithin, showed highest drug release of 94.048 % in 24 hrs and formulation F9 showed lowest drug release of 73.789 % in 16 hrs. Transdermal flux (J) of formulation F1 was found to be high (7.518±0.041μg/cm2.hr) as compared to other formulations and marketed preparation. Proniosomal formulation (F1), consisting of sodium cholate (concentration 3%) and cosolvent (isopropanol) attained highest penetrability effect, where sodium cholate and isopropanol induced significant changes in membrane permeability as they completely solubilised membrane phospholipids by sodium cholate micelles. In case of F1 formulation, percent inhibition was found to be 66.84%. Serum estimation of Ketorolac Tromethamine (KT) revealed that application of F1formulation produced 4-fold increase in peak plasma concentration within 12 hours and was maintained upto 24 hours as compared to marketed formulation. Eventually a significant in-vitro-in-vivo correlation was achieved and PN formulation of KT shows significant improvement in bioavailability of KT in systemic circulation when applied via topical route as compared to marketed gel preparation.