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 pharmacological applications a series of 7-([1,1′-biphenyl]-4-yl)-5-arylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-diones were synthesized and characterized using IR, ¹H, 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 radical scavenging activity. Halogen-substituted compounds showed more potent antimicrobial and anticancer activity than other derivatives in comparison 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 compound 5c as a promising anticancer agent against the human breast cancer MCF-7 cell line.

Keywords:

• Pyrido[2,3-d]pyrimidine
• antioxidant
• anticancer activity
• apoptosis
• molecular docking
• ADMET properties

Disclosure statement

No potential conflict of interest was reported by the author(s).