Paper Citing NAMD - Abstract
Sekhar, P. Nataraj; Reddy, L. Ananda; De Maeyer, Marc; Kumar, K. Praveen; Srinivasulu, Y. S.; Sunitha, M. S. L.; Sphoorthi, I. S. N.; Jayasree, G.; Rao, A. Maruthi; Kothekar, V. S.; Narayana, P. V. B. S.; Kishor, P. B. Kavi
Genome wide analysis and comparative docking studies of new diaryl furan derivatives against human cyclooxygenase-2, lipoxygenase, thromboxane synthase and prostacyclin synthase enzymes involved in inflammatory pathway
JOURNAL OF MOLECULAR GRAPHICS & MODELLING, 28:313-329, NOV 2009
In an effort to develop potent anti-inflammatory and antithrombotic drugs, a series of new 4-(2-phenyltetrahydrofuran-3-yl) benzene sulfonamide analogs were designed and docked against homology models of human cyclooxygenase-2 (COX-2), lipoxygenase and thromboxane synthase enzymes built using MODELLER 7v7 software and refined by molecular dynamics for 2 ns in a solvated layer. Validation of these homology models by procheck, verify-3D and ERRAT programs revealed that these models are highly reliable. Docking studies of 4-(2-phenyltetrahydrofuran-3-yl) benzene sulfonamide analogs designed by substituting different chemical groups on benzene rings replacing 1H pyrazole in celecoxib with five membered thiophene, furan, 1H pyrrole, 1H imidazole, thiazole and 1,3-oxazole showed that diaryl furan molecules showed good binding affinity towards mouse COX-2. Further, docking studies of diaryl furan derivatives are likely to have superior thromboxane synthase and COX-2 selectivity. Docking studies against site directed mutagenesis of Arg120Ala, Ser530Ala, Ser530Met and Tyr355Phe enzymes displayed the effect of inhibition of COX-2. Drug likeliness and activity decay for these inhibitors showed that these molecules act as best drugs at very low concentrations. (C) 2009 Elsevier Inc. All rights reserved.
