Isatin-Hydrazones with Multiple Receptor Tyrosine Kinases (RTKs) Inhibitory Activity and In-Silico Binding Mechanism

Recently, we have reported a series of isatin hydrazone, two them, namely, 3-((2,6-dichlorobenzylidene)hydrazono)indolin-2-one (1) and 3-((2-chloro-6-fluorobenzylidene)hydrazono)indolin-2-one (2) having potent cytotoxicity, showing cyclin-dependent kinases (CDK2) inhibitory activity bearing recommended drug likeness properties. Since both compounds (1 2) showed against CDK2, assumed it would also multiple receptor tyrosine (RTKs) activity. Considering those points, here, above-mentioned hydrazone 1 2 were synthesized using previously method for further investigation their potency on RTKs (EGFR, VEGFR-2 FLT-3) As expected, Compound exhibited excellent epidermal growth factor IC50 = 0.269 µM), vascular (VEGFR-2, 0.232 µM) FMS-like kinase-3 (FLT-3, 1.535 kinases. On the other hand, EGFR (IC50 0.369 0.266 FLT-3 0.546 A molecular docking study with EGFR, kinase suggested that act as type I ATP competitive inhibitors VEGFR-2, II non-competitive FLT-3.