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 (IC ₅₀ = 0.758, 0.400, and 0.524 nM) have lower IC ₅₀ values compared to clavulanic acid (IC ₅₀ = 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.