Synthesis, molecular docking simulation, and antimicrobial activities of novel fused pyrimidine systems linked to N-arylacetamide and vanillin units as novel hybrid molecules via Hantzsch and Biginelli reactions

Abstract

Bacterial infections pose a global issue, resulting in sickness and death, especially in underdeveloped nations. The challenge of resistance to current treatments is a significant worry in healthcare. Creating distinct molecules that do not engage with existing drugs is crucial for addressing resistance. In this context, a novel blend of hexahydro-[1,2,4]triazolo[5,1-b]quinazolines, tetrahydrobenzo[4,5]imidazo[2,1-b]quinazolines, and decahydropyrimido[4,5-b]quinolines linked to 2-methoxyphenoxy-N-arylacetamide moieties via Biginelli and Hantzsch reactions is disclosed. Spectroscopy elements and data were used to confirm the compositions of the new compounds. The antibacterial efficacy of all the synthesized compounds was evaluated against different bacterial strains. The antibacterial effectiveness of the synthesized compounds was evaluated against four distinct bacterial strains. Compound 22c exhibited the greatest inhibition zone (23 ± 0.7 mm) against Pseudomonas aeruginosa when compared to Gentamycin (21 ± 0.5 mm). Compounds 22a and 22c demonstrated identical lowest minimum inhibition concentrations (MIC), recorded at 156.3 µg/mL. Molecular docking studies revealed that compounds 22a-d exhibited high binding affinities to bacterial glycosyltransferase and β-ketoacyl-ACP-synthase III when compared to Gentamycin.