Molecular Docking and Biophysical Studies for Antiproliferative Assessment of Synthetic Pyrazolo-Pyrimidinones Tethered with Hydrazide-Hydrazones

Chemotherapy represents the most applied approach to cancer treatment. Owing frequent onset of chemoresistance and tumor relapses, there is an urgent need discover novel more effective anticancer drugs. In search for therapeutic alternatives treat disease, a series hybrid pyrazolo[3,4-d]pyrimidin-4(5H)-ones tethered with hydrazide-hydrazones, 5a–h, was synthesized from condensation reaction pyrazolopyrimidinone-hydrazide 4 arylaldehydes in ethanol, acid catalysis. vitro assessment antiproliferative effects against MCF-7 breast cells, unveiled that 5a, 5e, 5g, 5h were compounds exerted their cytotoxic activity through apoptosis induction G0/G1 phase cell-cycle arrest. To explore mechanism at molecular level, evaluated binding interactions two well-known targets, namely epidermal growth factor receptor (EGFR) G-quadruplex DNA structures. Molecular docking simulations highlighted high affinity towards EGFR. Circular dichroism (CD) experiments suggested 5a as stabilizer agent Kirsten ras (KRAS) oncogene promoter. light these findings, we propose pyrazolo-pyrimidinone scaffold bearing hydrazide-hydrazone moiety lead skeleton designing compounds.