Design and synthesis of novel N-benzyl-2,5-dihydro-1H-pyrrole-linked benzopyrimidine conjugates as antimicrobial agents: study combining in vitro and in silico analysis

Abstract

A new series of N-benzyl-2,5-dihydro-1H-pyrrole-linked benzopyrimidines 5 and 6 were synthesized via the 1,3-dipolar cycloaddition reaction of acetylenic dipolarophiles 3 and 4 with azomethine ylide generated in situ from N-(methoxymethyl)-N-(trimethylsilyl)benzylamine and evaluated for their in vitro antimicrobial activity. The structures of the prepared products were characterized using ¹H/¹³C NMR, IR, and ESI-HRMS techniques. Further, the synthesized compounds were assessed for their antibacterial activity against five types of pathogenic bacteria and three fungal strains. The results show that the degree of antimicrobial effect displayed by the synthesized compounds was variable. Notably, compounds 2a, 2d, 2f, 3e, 3h, 4a, 4d, 4f, 5a, 5b, 5d, 5f, 6b, and 6c showed high activity against the bacterial strains, with MIC values ranging from 15.12 to 15.62 μg mL⁻¹. Moreover, compounds 2a, 2f, 5a, 5b, 5d, 5g, and 5h exhibited promising antifungal activity against three Candida strains, with MIC values ranging from 62.5 to 125 μg mL⁻¹. In addition, molecular docking studies performed to identify the most effective antibacterial compounds against B. subtilis highlighted the high binding affinity of the synthesized compounds toward Bacillus subtilis YdiB (pdb: 5MVR).