Thiazole and Related Heterocyclic Systems as Anticancer Agents: A Review on Synthetic Strategies, Mechanisms of Action and SAR Studies.

BACKGROUND Cancer is the second leading cause of death throughout the world. Many anticancer drugs are commercially available, but lack of selectivity, target specificity, cytotoxicity and development of resistance lead to serious side effects. There have been several experiments going on to develop compounds with minor or no side effects. OBJECTIVE This review mainly emphasizes synthetic strategies, SAR studies, and mechanism of action for thiazole, benzothiazole, and imidazothiazole containing compounds as anticancer agents. METHODS Recent literature related to thiazole and thiazole-related derivatives endowed with encouraging anticancer potential is reviewed. This review emphasizes contemporary strategies used for the synthesis of thiazole and related derivatives, mechanistic targets, and comprehensive structural activity relationship studies to provide perspective into the rational design of high-efficiency thiazole-based anticancer drug candidates. RESULTS Exhaustive literature survey indicated that thiazole derivatives are associated with properties of inducing apoptosis and disturbing tubulin assembly. Thiazoles are also associated with the inhibition of NFkB/mTOR/PI3K/AkT and regulation of estrogen-mediated activity. Furthermore, thiazole derivatives have been found to modulate critical targets such as topoisomerase and HDAC. CONCLUSION Thiazole derivatives seem to be quite competent and act through various mechanisms. Some of the thiazole derivatives, such as compounds 29, 40, 62, and 74a with IC50 values of 0.05 μM, 0.00042 μM, 0.18 μM, and 0.67 μM, respectively not only have anticancer activity but they also have lower toxicity and better absorption. Therefore, some other similar compounds could be investigated to aid in the development of anticancer pharmacophores.