Design, Synthesis, Molecular Docking, and Biological Evaluation of 7-Phenyl-5-(thiophen-2-yl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-diones as Antibacterial Agents.

Background: New antibacterial agents are urgently needed as bacterial diseases, especially urinary tract infections (UTIs), are becoming more common, and antibiotic resistance is increasing.

Aims: This study aimed to design, synthesize, and conduct molecular docking and biological evaluation of pyrido[2,3-d]pyrimidine-2,4(1H,3H)-diones as antibacterial agents.

Methods: 7-Phenyl-5-(thiophen-2-yl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-diones were designed using an in silico approach. The designed compounds were synthesized using reported procedures. Molecular docking studies were carried out using the Maestro 12.9 module of Schrodinger software. QikProp module of the Schrodinger suite was used for in silico ADME evaluation of synthesized compounds. In vitro antibacterial activity of these compounds was assessed using the serial dilution method.

Results: Compounds MA-03 and MA-12 showed potent antibacterial activity with MIC values of 1.56, 3.125, 1.56, and 6.25 μg/ml and 1.56, 3.12, 6.25, and 3.12 μg/ml, respectively, against Bacillus subtilis, Staphylococcus aureus, Pseudomonas putida, and Escherichia coli using controls ciprofloxacin and amoxicillin (0.78, 0.39, 1.56 and 0.39 μg/ml and 0.78, 3.125, 3.125, and 1.56 μg/ml). All the synthesized compounds demonstrated higher binding affinities against bacterial proteins with reference to amoxicillin and ciprofloxacin.

Conclusion: All the compounds exhibited antibacterial activity against all the tested strains of bacteria with optimum ADME profile.