Synthesis, Molecular Docking of Phenolic Amides and 2, 3 Diphenylacrylamide

Abstract

A novel classes of hybrid molecules were synthesized where substituted phenolic acids and substituted 2, 3 diphenylacrylic acids (combretastatin analogue) were linked with phenastatin analogue through an amide linkage, respectively. In vitro study revealed that the novel amides (E)-3-(3,4-dihydroxyphenyl)-N-(4-(2,3,4- trimethoxybenzoyl) phenyl)acrylamide (9), 3,4,5-trihydroxy-N-(4-(2,3,4-trimethoxybenzoyl) phenyl)benzamide (14), and (E)-2,3-bis(4-hydroxyphenyl)-N-(4-(2,3,4-trimethoxybenzoyl)phenyl)acrylamide (20) were active against M. smegmatis with MIC value less than 50 µg mL−1, and a docking study showed those specific molecules were interacting with various amino acid residues of FabG4 of MTb. These novel amides might be useful for developing an alternative antibacterial agent which could control secondary infection, after a details SAR study. © 2025 Wiley-VCH GmbH.