Hybridization of isatin and benzoxazolinone via a diethyl spacer: a new scaffold for breast cancer drug discovery

Aim The present study mainly focused to design and synthesized isatin and benzoxazolinone hybrids via a diethyl linker and evaluate their anti-breast cancer activities.Materials and methods Five distinct types of isatin-benzoxazolinone derivatives were designed here using the diethyl chain as a linker, and in these molecules, the ketone group of isatin (IST) was treated with urea, thiourea, hydrazine, semicarbazide, and thiosemicarbazide resulting in the formation of corresponding schiff-base derivatives. The binding interactions of all five designed compounds were explored along with the reference ligands axitinib and sorafenib, with the vascular endothelial growth factor receptor-2 (VEGFR-2) (PDB ID: 4AG8) molecular docking and molecular dynamics (MD) simulations. BIT was then synthesized, characterized by IR, LCMS, 1H NMR, and further anticancer activity assessed against MCF-7 cell line using sorafenib as standard.Results Molecular docking revealed that compound BIT (hybrid in which ketone group of isatin clubbed with thiosemicarbazide) exhibited a docking score of −10.2 kcal/mol, surpassing the binding affinities of the reference ligands axitinib and sorafenib, highlighting its promising potential.Conclusion The BIT compound was evaluated, and the results indicated that it exhibited significant inhibitory activity against MCF-7 cells at a concentration of 30 mM.