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

Abstract

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.

Design of Promising Thiazoloindazole-Based Acetylcholinesterase Inhibitors Guided by Molecular Docking and Experimental Insights

“…Within the array of available heterocycles, indazoles and thiazoles stand out due to their diverse and significant pharmacological properties, rendering them a great interest in the realms of medicinal chemistry and drug discovery. Compounds incorporating indazole units are being investigated as potential candidates for use in anti-inflammatory, antifungal, antimicrobial, kinase, and nitric oxide synthase (NOS) inhibitors, as well as anticancer agents, among other applications. − Furthermore, the presence of thiazole moiety is considered relevant in the development of new drugs with potential anticancer, antibacterial, anti-inflammatory, analgesic, antitubercular, anti-Alzheimer, and antidiabetic properties. − Synthetic methodologies leading to the fusion of thiazoles with other heterocycles like carbazoles, indoles, and indazoles have also been reported to yield novel thiazoloheteroarenes with bioactive potential across various fields. , …”

Novel Benzothiazole Derivatives Synthesis and its Analysis as Diuretic Agents

“…Derivatives of 2-aminobenzothiazoles are reported to have diverse biological activities like cytotoxicity, antiinfammatory, analgesic, anthelmintic, antiviral, antidiabetic, antimicrobial, antileishmanial, anticonvulsant, Alzheimer's disease, and calcium channel blocking [3][4][5][6]. Te present study was carried out on 6-sulfonamide containing 2-aminobenzothiazole Schif bases derivatives as lead molecules of the study with the aid of docking for evaluating their diuretic activity, which is an adjutant therapy in treating hypertension [7][8][9].…”