Substitution of terminal amide with 1H-1, 2, 3-triazole: Identification of unexpected class of potent antibacterial agents. Issue 5 (1st March 2018)

• Record Type: Journal Article
• Authors: Bi, Fangchao; Ji, Shengli; Venter, Henrietta; Liu, Jingru; Semple, Susan J.; Ma, Shutao
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 5(2018)
• Page Start: 884
• Page End: 891
• Publication Date: 2018-03-01
• Subjects: 1H-1, 2, 3-Triazole -- Terminal amide -- Mimic -- Antibacterial agents -- In silico prediction; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.02.001
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: 1 H -1, 2, 3-triazole-containing 3-MBA analogues were prepared via isosteric replacement. The analogues exhibited better antibacterial activity than their amide precursor. The 1 H -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. Abstract: 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 1 H -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 1 H -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 1 H -1, 2, 3-triazole-containing analogues was observed, which could open new opportunities for the development of antibacterial agents.