| Summary: | Recently, we have reported a series of isatin hydrazone, two of them, namely, 3-((2,6-dichlorobenzylidene)hydrazono)indolin-2-one (<b>1</b>) and 3-((2-chloro-6-fluorobenzylidene)hydrazono)indolin-2-one (<b>2</b>) having potent cytotoxicity, showing cyclin-dependent kinases (CDK2) inhibitory activity and bearing recommended drug likeness properties. Since both compounds (<b>1</b> and <b>2</b>) showed inhibitory activity against CDK2, we assumed it would also have multiple receptor tyrosine kinases (RTKs) inhibitory activity. Considering those points, here, above-mentioned two isatin hydrazone <b>1</b> and <b>2</b> were synthesized using previously reported method for further investigation of their potency on RTKs (EGFR, VEGFR-2 and FLT-3) inhibitory activity. As expected, Compound <b>1</b> exhibited excellent inhibitory activity against epidermal growth factor receptor (EGFR, IC<sub>50</sub> = 0.269 µM), vascular epidermal growth factor receptor 2 (VEGFR-2, IC<sub>50</sub> = 0.232 µM) and FMS-like tyrosine kinase-3 (FLT-3, IC<sub>50</sub> = 1.535 µM) tyrosine kinases. On the other hand, Compound <b>2</b> also exhibited excellent inhibitory activity against EGFR (IC<sub>50</sub> = 0.369 µM), VEGFR-2 (IC<sub>50</sub> = 0.266 µM) and FLT-3 (IC<sub>50</sub> = 0.546 µM) tyrosine kinases. A molecular docking study with EGFR, VEGFR-2 and FLT-3 kinase suggested that both compounds act as type I ATP competitive inhibitors against EGFR and VEGFR-2, and type II ATP non-competitive inhibitors against FLT-3.
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