Synthesis & Characterization of 2-(substituted-phenyl)acetohydrazide Analogs, 1,3,4-oxadiazoles, and 1,2,4-triazine Ring Systems: A Novel Class of Potential Analgesic and Anti-Inflammatory Agents

Abstract

The new series of 2-(substituted-phenyl)acetohydrazides analogs, S-alkylated 5-substituted-1,3,4-oxadiazoles- 2-thione derivatives and 5-arylidene-3-substituted-1,2,4-triazines have been synthesized in good yields and characterized by IR, NMR, mass spectral and elemental analyses. All the synthesized compounds 4(a-d), 5(a-d), 7(a-b), and 8(a-f) are evaluated for their in vitro DPPH scavenging, antimicrobial activity, in vivo analgesic, anti-inflammatory activities. The results of the anti-inflammatory activity are supported by molecular docking study with mouse COX-1 (PDB ID: 2CZT) and COX-2 (PDB ID: 3LN1) enzymes to predict their putative interactions. Among all the assays conducted, the compounds 5-(4-bromophenyl)-3-(naphthalen-2-ylmethyl)-1,2,4-triazine (4d) and2-{[5-(diphenylmethyl)-1,3,4-oxadiazol-2- yl]sulfanyl}-N-(pyrazin-2-yl)acetamide (8a) have emerged as the most potent molecules. Keywords: Acid hydrazide analogs, antioxidant activity, analgesic activity, anti-inflammatory activity, antimicrobial activity, molecular docking study.