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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

Synthesis, Anti-inflammatory, Antimicrobial Potential and Molecular Docking Studies of 4,5-Disubstituted-1,2,4-Triazole Thioacetate Derivatives

Author(s): Muhammad Nouman Arif, Humaira Nadeem*, Rehan Zafar Paracha, Arif-ullah Khan, Muhammad Imran and Fawad Ali

Volume 16, Issue 7, 2019

Page: [734 - 745] Pages: 12

DOI: 10.2174/1570180815666180810122226

Abstract

Background: In the present study synthesis and biological assessment of nine new ethyl [(4,5-disubstituted- 4H-1,2,4-triazol-3-yl)sulfanyl]acetate derivatives 2(a-i) is performed.

Methods: The title compounds were characterized by their analytical and spectral data. All the synthesized compounds were screened for their in vivo anti-inflammatory activity using carrageenaninduced rat paw oedema method and in vitro antimicrobial activity. All the compounds exhibited good anti-inflammatory activity; especially compound 2h produced the maximum effect i.e., 62.5 % comparable to that of standard, diclofenac. The antimicrobial screening results indicated that some of the newly synthesized compounds showed good antibacterial activity, especially against Escherichia coli.

Results: All the synthesized thioacetate derivatives of triazoles were also studied for their interactions with the enzymes COX-I and COX-II, two important targets of inflammation pathway, through docking analysis. All the compounds showed good binding affinities with both the enzymes with a maximum value of -8.1 for 2e kcal/mol against COX-I.

Conclusion: Docking analysis predicted that our compounds reduce inflammation nonselectively by inhibiting both COX-I and COX-II of inflammatory pathway just like other nonselactive NSAIDS.

Keywords: 1, 2, 4-triazole thioacetate derivatives, biological evaluation, molecular docking, COX inhibitor, in vivo, in vitro, nonslactive NSAIDS

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