Substitution of terminal amide with 1H-1,2,3-triazole: Identification of unexpected class of potent antibacterial agents

[Display omitted] •1H-1,2,3-triazole-containing 3-MBA analogues were prepared via isosteric replacement.•The analogues exhibited better antibacterial activity than their amide precursor.•The 1H-1,2,3-triazole group served as a good mimic of the terminal amide group.•Potential target for these novel analogous was predicted using computational techniques. 3-Methoxybenzamide (3-MBA) derivatives have been identified as novel class of potent antibacterial agents targeting the bacterial cell division protein FtsZ. As one of isosteres for the amide group, 1,2,3-triazole can mimic the topological and electronic features of the amide, which has gained increasing attention in drug discovery. Based on these considerations, we prepared a series of 1H-1,2,3-triazole-containing 3-MBA analogues via isosteric replacement of the terminal amide with triazole, which had increased antibacterial activity. This study demonstrated the possibility of developing the 1H-1,2,3-triazole group as a terminal amide-mimetic element which was capable of both keeping and modulating amide-related bioactivity. Surprisingly, a different action mode of these new 1H-1,2,3-triazole-containing analogues was observed, which could open new opportunities for the development of antibacterial agents.