Rational Design, Synthesis, and Biological Evaluation of New Substituted Dihydropyrimidinones as Antibacterial Agents...

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.