In Silico Molecular Docking and In Vitro Antimicrobial Evaluation of Novel 2‐(4‐(3‐(4‐formylphenoxy)propyl)‐1H‐1,2,3‐triazol‐1‐yl)‐N‐Phenylacetamides

Abstract

AbstractA series of new 2‐(4‐(3‐(4‐formylphenoxy)propyl)‐1H‐1,2,3‐triazol‐1‐yl)‐N‐phenylacetamides was successfully designed and synthesized via the click reaction. The alkyne agent 4‐(pent‐4‐yn‐1‐yloxy) benzaldehyde was prepared from 4‐hydroxybenzaldehyde and 5‐chloropent‐1‐yne. Meanwhile, the 2‐azido‐N‐phenylacetamides were obtained by the azidation of 2‐chloro‐N‐phenylacetamides which were formed from aromatic amine and chloroacetyl chloride. The novel compounds were characterized by FT‐IR, 1H/13C NMR, HRMS, MS, and elemental analysis, and evaluated for their in vitro antimicrobial activity against Acinetobacter baumannii, Carbapenem resistant pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter aerogenes, Vancomycin resistant enterococcus faecium and Methicillin resistant staphylococcus aureus bacterial strains, as well as Candida albicans and Aspergillus niger fungal strains. Some of the compounds revealed significant potential activity compared to the reference drugs. Compound 4 h showed the highest activity (MIC=133 μM, 106 μM, 133 μM, 106 μM) against Ac. Baumannii, Klebsiella pneumoniae, Enterobacter aerogenes, and Methicillin‐resistant Staphylococcus aureus (MRSA), respectively, as antibacterial and against Candida albicans (MIC=534 μM) and Aspergillus niger (MIC=1,068 μM) as antifungal. Using in silico molecular docking and ADMET studies, the compounds with the highest potential activity were examined. The results showed strong receptor site binding affinity and indicated promising antimicrobial potential.