Rational Design, Synthesis, and Biological Evaluation of New Substituted Dihydropyrimidinones as Antibacterial Agents and β‐Lactamase Inhibitors

Abstract

A series of new substituted 1,6‐dihydropyrimidinones was designed, synthesized, and biologically evaluated as potential antibacterial candidates and β‐lactamase enzyme inhibitors. All the synthesized compounds were tested for their antibacterial activity against Staphylococcus aureus, Bacillus subtilis as a gram‐positive species whereas Pseudomonas aeruginosa as a gram‐negative species was utilized. Most of the compounds exhibited moderate antibacterial activity compared to the reference drug amoxicillin. Furthermore, clinical antibacterial tests were conducted on β‐lactamase resistant strains, including Acinetobacter baumannii, Bacillus subtilis, and Staphylococcus aureus. Results indicated that the candidate compounds possess potentiation effect, indicating their role as effective β‐lactamase enzyme inhibitors. Whereas in‐vitro assay performed on β‐lactamase enzymes revealed that compounds 3d, 3i, and 7b (IC50 = 0.758, 0.400, and 0.524 nM) have lower IC50 values compared to clavulanic acid (IC50 = 0.934 nM). These findings suggested that compounds 3d, 3i, and 7b are considered as promising hits for further exploration of potent and selective β‐lactamase inhibitors.