Present study reports the development of novel pyridopyrimidine derivatives as biotin carboxylase inhibitors with potent antibacterial activity. These compounds were designed to avoid possibility of resistance development. Accordingly eighteen compounds were synthesised and characterized on the basis of spectral data. These compounds were tested for their antibacterial potential by the enzyme kinetic assay against the biotin carboxylase. The minimum inhibitory concentration (MIC) and single step resistance studies were also performed. Compound 2-((2-Phenylpyrido[2,3-d] pyrimidin-4-yl)amino)phenol (6o) showed promising activity in biotin carboxylase inhibition with low MIC. It showed molecular docking score of -7.96, this compound showed formation of hydrogen bonds with the active site residues and van Der Walls interactions. The MIC of compounds under investigation was in the rage of 2-5µg/mL over most of the strains studied. It also showed the mutant selection windows of around five which is better than the reference compound rifampin. This compound 6o can be studied further and developed into a potential antibacterial lead molecule.

We report a novel scaffold of N-substituted 2-phenylpyrido(2,3-d)pyrimidine derivatives with potent antibacterial activity by targeting this biotin carboxylase enzyme. The series of eighteen N-substituted 2-phenylpyrido(2,3-d)pyrimidine derivatives were synthesized, characterized and further molecular docking studied to determine the mode of binding and energy changes with the crystal structure of biotin carboxylase (PDB ID: 2V58) was employed as the receptor with compounds 6a-r as ligands. The results obtained from the simulation were obtained in the form of dock score; these values represent the minimum energies. Compounds 6d, 6l, 6n, 6o, 6r and 6i showed formation of hydrogen bonds with the active site residues and van Der Walls interactions with the biotin carboxylase enzyme in their molecular docking studies. This compound can be studied further and developed into a potential antibacterial lead molecule.

We report a novel scaffold of 2-phenylpyrido[2,3-d]pyrimidine derivatives designed as structural analogues of dinaciclib. Sixteen derivatives were synthesised and evaluated for their CDK2/5 inhibition activity. Compounds 4-(2-(3-methoxybenzylidene)hydrazineyl)-2-phenylpyrido[2,3-d]pyrimidine (7i) and 4-(2-(3-nitrobenzylidene)hydrazineyl)-2-phenylpyrido[2,3-d]pyrimidine (7n) show promising IC50 and kinase selectivity. These compounds also show moderate anti-proliferative activity in the colon cancer HCT116 and breast cancer MCF7 cell lines. In molecular docking studies with CDK2, compounds 7i and 7nshow binding similar to dinaciclib.