Computational Insights into Quinazoline-Isatin Conjugates as VEGFR Inhibitors: Anticancer Candidates

Abstract

Background:

As one of the most significant contributors to global mortality, cancer continues to stimulate intensive investigations into the anticancer and free radical-scavenging properties of new conjugates as potential therapeutic agents for advanced cancer treatment strategies.

Method:

This study reports the rational design and systematic assessment of four quinazoline-isatin hybrids (HK1-HK4) as potential VEGFR tyrosine kinase inhibitors through molecular docking and dynamic simulations, with binding affinities evaluated based on docking scores and RMSD values.

Results:

SwissADME analysis confirmed excellent drug-likeness with complete Lipinski's Rule of Five compliance (MW: 347-401 Da, iLOGP: -0.44 to 1.02). All conjugates showed high GI absorption, no BBB penetration, and 0.55 bioavailability scores. Molecular docking revealed superior VEGFR binding affinities (-7.8 to -9.681 kcal/mol), with HK1 demonstrating optimal binding (-9.681 kcal/mol) through interactions with Lys868, Cys919, and Asp1046.

Conclusion:

The quinazoline-isatin hybrids demonstrate excellent drug-likeness with complete Lipinski compliance and superior VEGFR binding. These promising computational results warrant experimental validation through in vitro enzymatic assays and cytotoxicity studies to advance clinical anticancer drug recognition.