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Sharma M.C.,Devi Ahilya University | Sharma S.,Choudhary Dilip Singh Kanya Mahavidyalaya | Bhadoriya K.S.,Rc Patel Institute Of Pharmaceutical Education And Research
Journal of Saudi Chemical Society | Year: 2012

The quantitative structure-activity relationship (QSAR) analyses including 2D-QSAR, Group-based QSAR (GQSAR), 3D-QSAR using kNN-MFA methodology and pharmacophore studies were carried out for a series of tetrazole and sulfonamide analogs of imidazo[4,5-b]pyridine to find out the structural requirements of their angiotensin AT 1 receptor antagonistic activities. The multiple linear regression (MLR) and kNN-MFA methods coupled with simulated annealing (SA) feature selection method were applied to derive QSAR models which were further validated for statistical significance and predictive ability by internal and external validation. The statistically significant best 2D-QSAR model 1 having r 2 = 0.8762 and q 2 = 0.7732 with pred_r 2 = 0.7563 was developed by SA-MLR and the best Group-based QSAR (GQSAR) model having r 2 = 0.7806 and q 2 = 0.7180 with pred_r 2 = 0.7885 was developed by SA-MLR. Molecular field analysis (MFA) was used to construct the best 3D-QSAR model using SA-kNN method, showing good correlative and predictive capabilities in terms of q 2 = 0.8271 and pred_r 2 = 0.7991. Five chemical feature based several pharmacophore models were generated using VLife MDS MolSign Module and the best pharmacophore model is selected on the basis of the lowest RMSD value, containing one aromatic carbon center, one aliphatic carbon center, one hydrogen bond donor and two hydrogen bond acceptor features. These combined studies for a series of tetrazole and sulfonamide analogs of imidazo[4,5-b]pyridine provide guidance for further lead optimization and designing of novel potent antihypertensive agents. © 2012.


Nerkar P.P.,Rc Patel Institute Of Pharmaceutical Education And Research | Gattan S.G.,iversity
Journal of Materials Science: Materials in Medicine | Year: 2012

Venlafaxine is a newer antipsychotic drug which shows first pass effect. Cress seed is also called as garden cress or green salad. This study examined the mechanical (gel strength, adhesiveness) and rheological properties of cress seed mucilage based gels that contain different ratios of carbopol 934 P (0.5-1.5%). In addition, diffusion of venlafaxine from gel formulations was evaluated. The selected formulation was further analyzed for pharmacokinetic parameters in rabbits. All formulations exhibited pseudoplastic flow with thixotropy. Formulation F5 showed the C max of 24.19 ± 0.72 ng/ml by buccal route of administration and 17.98 ± 1.15 ng/ml by oral route of administration. The bioavailability of F5 by buccal route was 54.44% and that of by oral route was 39.60%. A combination of the cress seed mucilage and carbopol 934 P resulted in a prolonged and higher venlafaxine delivery by buccal route of administration. © 2012 Springer Science+Business Media, LLC.


Ganorkar S.B.,Rc Patel Institute Of Pharmaceutical Education And Research
Bioorganic and Medicinal Chemistry Letters | Year: 2012

Novel 3-substituted-1-aryl-5-phenyl-6-anilino-pyrazolo[3,4-d]pyrimidin-4- ones of pharmacological significance were synthesized by the reaction of ethyl-(5-amino-3-methylthio-1-aryl-5-phenyl-2H-pyrazole)-4-carboxylates 3a-c with S-methyl diphenyl thiourea independently to produce 1-aryl-3-thiomethyl-5- phenyl-pyrazolo[3,4-d]pyrimidines 4a-c in DMF with catalytic amount of K 2CO3, which on further treatment with different aromatic amines independently under same reaction conditions generated for compounds 5a-l. The compounds were screened for the anti-inflammatory activity and evaluated for ulcerogenic potential. The compounds 5i exhibited superior anti-inflammatory activity in comparison with diclofenac sodium and comparable activity with celecoxib at a dose of 25 mg/kg. The other compounds 4c, 5c, 5f and 5l were found as active with inhibition of edema in the range of 35-39 after 3 h of administration of test compounds. The ulcerogenic potential of active compounds was observed to be quite lesser as compared to standard. COX-2 docking score of the active compound 5i was found to be better than standard celecoxib. © 2012 Elsevier Ltd. All rights reserved.


Sharma M.C.,Devi Ahilya University | Sharma S.,Choudhary Dilip Singh Kanya Mahavidyalaya | Bhadoriya K.S.,Rc Patel Institute Of Pharmaceutical Education And Research
Journal of Saudi Chemical Society | Year: 2013

The present paper is an attempt in this direction seeking for the development and comparison of QSAR models of 4,5,6,7-Tetrabromobenzimidazole by different feature selection methods, which ultimately establishes the superiority of the simulated annealing-based models. Two Dimensional and Three Dimensional Quantitative Structure-Activity Relationship (QSAR) studies were performed for correlating the chemical composition of 4,5,6,7-Tetrabromobenzimidazole analogs and their Protein Kinase CK2 inhibitors using two widely used techniques, viz. simulated annealing (SA) and genetic algorithm (GA) that have been applied for descriptor optimization. 2D-QSAR modeling using simulated annealing (SA) and genetic algorithm (GA) based partial least square methods identified some important topological and electrostatic descriptors as important factors for activity. The validated 2D models constructed with H-count, potential surface area, SaasCE-index and SAAverage Hydrophobicity descriptors yielded the cross-validated correlation coefficient of 0.8376, shows that the models have sufficient predictive ability. The three-dimensional QSAR technique identifies a suitable model obtained by simulated annealing and genetic algorithm partial least square method leading to Protein Kinase CK2 Inhibitor prediction. The influences of steric, electrostatic and hydrophobic field effects generated by the contribution plot are analyzed and discussed. Molecular field analysis was used to construct the best 3D-QSAR model using the SA-PLS method, showing good correlative and predictive capabilities in terms of q2 = 0.7496 and pred_r2 = 0.7809. The aliphatic/aromatic of the important feature in the molecule, which is also, present sides in the molecule near to 4,5,6,7 sites. Both two- and three-dimensional QSAR analyses of such derivatives provide important structural insights for designing potent Protein Kinase CK2 drugs. © 2013.


Noolvi M.N.,Shree Dhanvantary Pharmacy College | Patel H.M.,Rc Patel Institute Of Pharmaceutical Education And Research
European Journal of Medicinal Chemistry | Year: 2012

Novel derivatives of 2-amino benzothiazoles 4(a-j) have been synthesized and tested for their antitumor activity using National Cancer Institute (NCI) disease oriented antitumor screen protocol against nine panel of cancer cell lines. Among the synthesized compounds, two compounds were granted NSC code and screened at National Cancer Institute (NCI)-USA for anticancer activity at a single high dose (10-5 M) and five dose in full NCI 60 cell panel. Among the selected compounds, 7-chloro-N-(2,6-dichlorophenyl)benzo[d]thiazol-2- amine (4i) with GI50 values of 7.18 × 10-8 M against Non-Small Cell HOP-92 Lung Cancer cell line proved to be the most active members in this study. Virtual screening was carried out through docking the designed compounds into the ATP binding site of epidermal growth factor receptor (EGFR) to predict if these compounds have analogous binding mode to the EGFR inhibitors. © 2012 Elsevier Masson SAS. All rights reserved.

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