شناسایی و مقایسه اثر ترکیبات الگو به عنوان مهارکننده های جدیدCOX-2 به کمک تکنیک های محاسباتی طراحی دارو

خلاصه فارسی

ترکیبات جدید برای مهار آنزیم سیکلواکسیژناز-2 با اثر ضد التهابی به کمک روشهای محاسباتی طراحی دارو شناسایی و معرفی شد.

عنوان انگليسی

Identification and comparing the effect of lead compounds as novel COX-2 inhibitors using computer-aided drug design techniques

خلاصه انگلیسی

In an attempt to identify potential COX-2 inhibitors, a multi-step virtual screening strategy was performed on a series of compounds. For this purpose, ZINC database was screened on the basis of 50% structural similarity with celecoxib and indomethacin as the representative of COX-2 and COX-1/COX-2 inhibitors, respectively. Selected molecules were subjected to various filters such as Lipinski's rule of five and also several ADME parameters. Toxicity risk of molecules was approximated via in silico methods. Moreover, COX-2 inhibitory activities of the selected compounds were predicted using PASS program. Molecular docking was performed to improve the accuracy of screening and also to find the details of the interactions of the hit compounds with the active site. Finally, MD simulations on top-ranked structures ZINC_1130464, ZINC_3181760, ZINC_33402495 and celecoxib were carried out with COX-2. Furthermore, RMSD, RMSF, hydrogen binds, Rg and energy analysis during MD simulation certainly indicated the stable binding of selected compounds with COX-2 structure. Moreover, docking and MD results revealed that hydrophobic contacts and optimum hydrogen bonds were determinant factors in the interactions of in silico hits and COX-2.

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