Conjugate and Regiochemical Addition of Aminoazoles to 2-(4-(2,2-Dicyanovinyl)phenoxy)-N-phenylacetamide affording fused pyrimidines linked to phenoxy-N-arylacetamide: Antibacterial activity, molecular docking, and DNA binding studies

A facile, and efficient regiochemical synthesis of 7-amino [1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitriles, or 4-aminobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carbonitriles that are linked to phenoxy-N-arylacetamide moieties has been developed. The products are formed via the conjugate additions of exo-NH2 and ring-NH groups of the aminoazoles (3-amino[1,2,4]triazole, and 1H-benzo[d]imidazol-2-amine) to the 2-(4-(2,2-dicyanovinyl)phenoxy)-N-phenylacetamide. Well diffusion method was utilized to assess the antibacterial capabilities of the synthesized compounds (11a-d and 21a-d) against different bacterial strains, and it was found that 21c was the most potent. In accordance with experimental results, the antibacterial molecular docking findings revealed that 21c has remarkable binding capabilities toward different antibiotic-target proteins (PDB IDs: 4H8E, 4C13, 1JIJ, and 1AJ0). Upon investigating the DNA binding characteristics using absorption spectroscopy, the intrinsic binding constant for compound 21c was found to be 2.64 × 104 M−1, suggesting that it has a good potential for DNA binding.