Virtual screening for finding novel COX-2 inhibitors as antitumor agents

Badieyan, Z. S. and Moallem, S. A. and Mehri, S. and Shahsavand, S. and Hadizadeh, F. (2012) Virtual screening for finding novel COX-2 inhibitors as antitumor agents. Open Medicinal Chemistry Journal, 6 (1). pp. 15-19.

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Abstract

The cyclooxygenase-2 (COX-2) enzyme binds to arachidonic acid resulting in the release of metabolites that induce pain and inflammatory responses. Recent studies have shown that strong COX-2 expression is highly correlated with increased tumor risk. Therefore, the development of potent COX-2 inhibitors to relieve pain and treat cancers requires further investigation. We used virtual screening to find three COX-2 inhibitors (Phar-95239, T0511-4424 and Zu- 4280011) from a huge zinc database containing 2000000 compounds. The effects of the compounds on COX-2 were compared to those on COX-1 using a colorimetric COX (ovine) screening assay kit. The selectivity index, the ratio of IC50 for COX-1 inhibition to that of COX-2, calculated were MTT assay was used to evaluate the cytotoxic activity of the compounds using different dilutions. The IC50 values were calculated. Based on the results of the MTT assay, the IC50 values for compounds Phar-95239, T0511-4424 and Zu-4280011 were 178.52, 143 and 97.61 μM, respectively, and the selectivity indices of the compounds were 11.36, 12.20 and 20.03, respectively. These results indicated a relationship between the selectivity index and anticancer activity. Zu-4280011 displayed the highest selectivity index and the best results in the MTT assay among selected componds. © Badieyan et al.

Item Type: Article
Additional Information: Cited By :6 Export Date: 16 February 2020 Correspondence Address: Moallem, S. A.; Pharmaceutical Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; email: moallem@mums.ac.ir
Uncontrolled Keywords: Cyclooxygenase MTT Selectivity index Virtual Screening Zinc database 4 5 (4 bromophenyl) 3 trifluoromethyl 1h pyrazol 1 ylbenzenesulfonamide antineoplastic agent celecoxib cyclooxygenase 1 cyclooxygenase 2 cyclooxygenase 2 inhibitor phar 95239 t 0511 4424 unclassified drug zu 4280011 antineoplastic activity article cell assay cell strain MCF 7 colorimetry concentration response controlled study data base dilution drug cytotoxicity drug screening drug selectivity drug structure enzyme inhibition enzyme specificity human human cell IC 50 in vitro study molecular docking priority journal virtual reality
Subjects: QV pharmacology
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib5 lib5
Date Deposited: 12 May 2020 06:47
Last Modified: 12 May 2020 06:47
URI: http://eprints.mums.ac.ir/id/eprint/18772

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