Synthesis and Evaluation of Thiazolyl-indole-2-carboxamide Derivatives as Potent Multitarget Anticancer Agents
Njood M. Saadan, Wahid U. Ahmed, Adnan A. Kadi, Maha S. Almutairi, Reem I. Al-Wabli, A. F. M. Motiur Rahman
Abstract
High Resolution Image Download MS PowerPoint Slide Cancer is a complex disease driven by the dysregulation of multiple signaling pathways and cellular processes. The development of compounds capable of exerting multitarget actions against these key pathways involved in cancer progression is a promising therapeutic approach. Here, a series of novel ( E / Z )- N -(4-(2-(2-(substituted)hydrazineyl)-2-oxoethyl)thiazol-2-yl)-1 H -indole-2-carboxamide derivatives ( 6a – 6z ) were designed, synthesized, and evaluated for their biological activity. Compounds 6e, 6i, 6q, 6v, 7a, and 7b exhibited exceptional cytotoxicity against various cancer cell lines, particularly 6i (IC 50 = 6.10 ± 0.4 μM against MCF-7 cell lines) and 6v (IC 50 = 6.49 ± 0.3 μM against MCF-7 cell lines). These potent compounds inhibited key protein kinases like EGFR, HER2, VEGFR-2, and CDK2, induced cell cycle arrest at the G2/M phase, and promoted apoptosis. Docking studies revealed improved binding affinity of 6i and 6v with target proteins compared to reference drugs. These findings highlight the promising potential of 6i and 6v as multitarget cancer therapeutics deserving further development.