IN-SILICO MOLECULAR DOCKING AND ADMET PREDICTIONS OF PYRIDO[2,3-D]PYRIMIDINE-2,4(1H,3H)-DIONE ANALOGUES AS PROMISING ANTIMICROBIAL, ANTIOXIDANT AND ANTICANCER AGENTS

Abstract

Pyridopyrimidine are heterocyclic molecules enclosing fused pyridine and pyrimidine rings. Owing to its fascinating core structure and pharmaco- logical applications a series of 7-([1,10-biphenyl]-4-yl)-5-arylpyrido[2,3-d]pyr- imidine-2,4(1H,3H)-diones were synthesized and characterized using IR, 1 H, 13C NMR and Mass spectral techniques. The antibacterial, antioxidant and anticancer activities were investigated for the synthesized compound 5a- 5f. Compounds with electron-donating groups showed excellent free rad- ical scavenging activity. Halogen-substituted compounds showed more potent antimicrobial and anticancer activity than other derivatives in com- parison with their respective standards. Based on the IC50 value obtained from anticancer activity, 5c was further analyzed for apoptosis by AO/EB staining method. The findings suggested early apoptosis in the MCF-7 cell line. Molecular Docking studies of the synthesized compounds were performed with Kinase 1 inhibitors (PDB id: 2YEX), 5c exposed good docking results with minimum binding energy. Further, these compounds were acknowledged as orally active drug candidates from in-silico ADMET studies. Computational analysis supports biological findings indicating com- pound 5c as a promising anticancer agent against the human breast cancer MCF-7 cell line.