Novel series of 1,2,3-triazolyl-acetamide scaffolds: Synthesis, biological activity and computational molecular modeling

A novel series of 1,2,3-triazolyl-acetamide derivatives 9 were synthesizsed starting from N -(2,4-difluoro-3(methylthio)phenyl)but-3-ynamide and 2-azido- N -phenylacetamide. Structures of final compounds were confirmed by their 1 H NMR, 13 C NMR, IR, and mass spectral analysis. All new synthesised compounds were evaluated for their antibacterial activity against Gram ( + ve) and Gram (-ve) microorganisms. Antibacterial activity of compounds 9h, 9c, 9d, and 9i (MICs = 4.0, 3.8, 3.2, 6.7 mu g/mL) were the most potent inhibitory active against K. pneumoniae, S. aureus, S. pneumoniae, E. coli microorganisms respectively. We explored the probable key active site and binding mode interactions in carotenoid dehydrosqualene synthase from S. aureus complexed with bisphosphonate BPH-70 0 (2ZCS) protein and ligand 9i possesses highest hydrogen bonding amino acid interactions Ser21(2.86 A, 3.16 A), Lys17(2.91 A), Lys20(2.76 A), Lys17(2.13 A), Ser21(1.87 A). Scaffolds 9b, 9j and 9i exhibited highest potency with drug likeness score 0.84, 0.77 and 0.68 and processing Lipinski's rule of five as good oral bioavailability drugs.(c) 2022 Elsevier B.V. All rights reserved.

Automated summary

A novel series of 1,2,3-triazolyl-acetamide derivatives were synthesized and their structures were confirmed by various analyses. The compounds exhibited strong antibacterial activity against different microorganisms, with compounds 9h, 9c, 9d, and 9i showing the most potent inhibitory effects on K. pneumoniae, S. aureus, S. pneumoniae, and E. coli, respectively. The study also explored the interaction between the compounds and a target protein, providing insights into the key active site and binding mode.