One-Pot Synthesis of spiro(indoline-3,4′-pyrazolo[3,4-b]pyridine)-5′-carbonitriles As p53-MDM2 Interaction Inhibitors

Abstract

Compound 4d exhibited potent and broad spectrum of antiproliferative activity with full panel GI₅₀ (MG-MID) value of 3.97 μM. Compounds 4d and 4i inhibited p53-MDM2 protein-protein interaction with IC₅₀ = 52.1 and 95.2 nM, respectively. Compound 4d inhibits the expression of wild p53 in MCF-7 more than mutant p53 in MDA-MB231 at the molecular level. Molecular docking studies illustrated the possible interaction of the target spiro-oxindoles with the p53 binding site on MDM2.