Quinazolin-4(3<i>H</i>)-one based potential multiple tyrosine kinase inhibitors with excellent cytotoxicity

A series of quinazolin-4(3H)-one derivatives were synthesised and evaluated for their cytotoxicity against human Caucasian breast adenocarcinoma (MCF-7) ovarian carcinoma (A2780) cell lines. Cytotoxicity the most tested compounds was 2- to 30-fold more than positive control lapatinib (IC50 2j = 3.79 ± 0.96; 3j 0.20 0.02; 5.9 0.74) MCF7 lines except two 2 b 15.72 0.07 2e 14.88 0.99). On other hand, 4 ? 87 folds 3a 3.00 1.20; 3 g 0.14 0.03) 12.11 1.03) A2780 compound 16.43 1.80). Among derivatives, potent cytotoxic 2f-j 3f-j investigated molecular mechanism action. Inhibitory activities multiple tyrosine protein kinases (CDK2, HER2, EGFR VEGFR2) enzymes. As expected, all showed comparable inhibitory activity those tested, especially, 2i 3i CDK2, kinases. Therefore, docking analysis performed, it revealed that act as ATP non-competitive type-II inhibitor CDK2 kinase enzymes competitive type-I However, in case inhibitor. Docking results known inhibitors compared with found are superior interactions. In addition, silico drug likeness properties better predicted ADME values lapatinib.