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Sci. Pharm. 2010, 78(2), 195-214; doi:10.3797/scipharm.0912-19

Pharmacophore Elucidation and Molecular Docking Studies on 5-Phenyl- 1-(3-pyridyl)-1H-1,2,4-triazole-3-carboxylic Acid Derivatives as COX-2 Inhibitors

1
Department of Pharmaceutical Chemistry, Martin-Luther-Universität Halle-Wittenberg, 06120 Halle, Germany
2
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut-71527, Egypt
3
Pharmaceutical Technology and Manufacturing Center, College of Pharmacy, King Saud University Al Ryiadh, Kingdom of Saudi Arabia, P. O. Box 2457, Riyadh, 11451, Kingdom of Saudi Arabia
*
Author to whom correspondence should be addressed.
Received: 20 December 2009 / Accepted: 18 March 2010 / Published: 19 March 2010
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Abstract

A set of 5-phenyl-1-(3-pyridyl)-1H-1,2,4-triazole-3-carboxylic acid derivatives (16–32) showing anti-inflammatory activity was analyzed using a threedimensional qualitative structure-selectivity relationship (3D QSSR) method. The CatalystHipHop approach was used to generate a pharmacophore model for cyclooxygenase-2 (COX-2) inhibitors based on a training set of 15 active inhibitors (1–15). The degree of fitting of the test set compounds (16–32) to the generated hypothetical model revealed a qualitative measure of the more or less selective COX-2 inhibition of these compounds. The results indicate that most derivatives (16, 18, 20–25, and 30–32) are able to effectively satisfy the proposed pharmacophore geometry using energy accessible conformers (Econf < 20 kcal/mol). In addition, the triazole derivatives (16–32) were docked into COX-1 and COX-2 X-ray structures, using the program GOLD. Based on the docking results it is suggested that several of these novel triazole derivatives are active COX inhibitors with a significant preference for COX-2. In principle, this work presents an interesting, comprehensive approach to theoretically predict the mode of action of compounds that showed anti-inflammatory activity in an in vivo model.
Keywords: Catalyst; COX; GOLD; Docking; Pharmacophore Catalyst; COX; GOLD; Docking; Pharmacophore
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

LINDNER, M.; SIPPL, W.; RADWAN, A.A. Pharmacophore Elucidation and Molecular Docking Studies on 5-Phenyl- 1-(3-pyridyl)-1H-1,2,4-triazole-3-carboxylic Acid Derivatives as COX-2 Inhibitors. Sci. Pharm. 2010, 78, 195-214.

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