Synthesis, Characterization of Novel N'(2-Phenoxyacetyl)Nicotinohydrazide and N'(2-Phenoxyacetyl)Isonicotinohydrazide Derivatives as Anti-Inflammatory and Analgesic Agents

Abstract

A new derivatives of isonicotinohydrazide 9 (a-e) and 10(a-e) were designed, synthesized, characterized based on the different spectroscopic analysis FT-IR, -1H, -13C-NMR, mass spectra, and also elemental-analyses, and identified as a remarkable anti-inflammatory along with analgesic effect. In-vitro and in-vivo anti-inflammatory and analgesic actions were performed using analgesic acetic acid-induced squirming and Hot plate latency tests using male Swiss albino mice. The study was supported by the in-silico and ADMET approaches. Among the series, compound (10e) showed the highest IC50 value for COX-1 inhibition, whereas compounds (9e) and (10e) exhibited the highest COX-2 SI. Further, in silico studies provide a putative bind site for the potent compound in a three-dimensional geometrical view. The results revealed that the title compound (10e) with bromo group exhibited potent COX-2 inhibitor at different times which is on par with the normal drug used in the assay system. Substitution of halogens at N’(2-phenoxyacetyl)nicotinohyrazide showed (10e) potent analgesic outcome on acetic acid-induced squirming response and thermal pain among the series 9(a-e) and 10(a-e). The overall pharmacological result suggests that the newly synthesized compounds possess good anti-inflammatory along with analgesic-activity which was evaluated through in-vitro, in-vivo, and --silico studies.

Terminal Phenoxy Group as a Privileged Moiety of the Drug Scaffold—A Short Review of Most Recent Studies 2013–2022

“…Pallavi et al obtained novel N-(2-phenoxyacetyl) isonicotinohydrazide derivatives as anti-inflammatory and analgesic agents [ 132 ]. Cyclooxygenases 1 and 2 (COX-1 and COX-2) are key enzymes for the maintenance of health and injury.…”

“…Authors stated that bromo substituent at the para position at phenoxy moiety improved selectivity index, and it was found in the most active compound. A molecular docking study of binding ( 70 ) with COX-2 revealed π–π interaction between the phenoxy group and TYR385 and TRP387 [ 132 ] ( Figure 24 ).…”