Novel carbazolyl–thiazolyl–chromone and carbazolyl–thiazolyl–pyrazole hybrids: synthesis, cytotoxicity evaluation and molecular docking studies

Abstract

A simple synthetic method was performed to design a novel series of polycyclic systems consisting of carbazole–thiazolidinone–chromone hybrids 4a–e and carbazole–thiazolidinone–pyrazole hybrids 5a–e in excellent yields. The methodology depended on the one-pot four-component reaction of 3-amino-9-ethylcarbazole, substituted isothiocyanates, ethyl bromoacetate and 6-methyl-3-formylchromone in ethanol under ultrasound waves at 50 °C to give the carbazole–thiazolidinone–chromone hybrids 4a–e. The latter isolated products were treated with hydrazine hydrate in ethanol under ultrasound waves at 50 °C affording the corresponding carbazole–thiazolidinone–pyrazole hybrids 5a–e. Spectral and analytical data confirmed the structures of all the synthesized compounds. The target compounds were screened for their in vitro anticancer activities against HCT116, PC3 and HepG2 cancer cell lines using the standard SRB method. Fortunately, both compounds 5d and 5e were the most active against all cancer cell lines compared with doxorubicin and can be promising anticancer agents. Both bioactive products 5b and 5e were studied by the molecular docking to see how they bind with VEGFR-2 receptor. The results indicated that those compounds exhibited high affinities towards VEGFR-2 and established remarkably similar interactions to those of the powerful VEGFR-2-KDR.