2-Aminobenzothiazoles in anticancer drug design and discovery

Cancer is one of the major causes of mortality and morbidity worldwide. Substantial research efforts have been made to develop new chemical entities with improved anticancer efficacy. 2-Aminobenzothiazole is an important class of heterocycles containing one sulfur and two nitrogen atoms, which is associated with a broad spectrum of medical and pharmacological activities, including antitumor, antibacterial, antimalarial, anti-inflammatory, and antiviral activities. In recent years, an extraordinary collection of potent and low-toxicity 2-aminobenzothiazole compounds have been discovered as new anticancer agents. Herein, we provide a comprehensive review of this class of compounds based on their activities against tumor-related proteins, including tyrosine kinases (CSF1R, EGFR, VEGFR-2, FAK, and MET), serine/threonine kinases (Aurora, CDK, CK, RAF, and DYRK2), PI3K kinase, BCL-X_L, HSP90, mutant p53 protein, DNA topoisomerase, HDAC, NSD1, LSD1, FTO, mPGES-1, SCD, hCA IX/XII, and CXCR. In addition, the anticancer potentials of 2-aminobenzothiazole-derived chelators and metal complexes are also described here. Moreover, the design strategies, mechanism of actions, structure-activity relationships (SAR) and more advanced stages of pre-clinical development of 2-aminobenzothiazoles as new anticancer agents are extensively reviewed in this article. Finally, the examples that 2-aminobenzothiazoles showcase an advantage over other heterocyclic systems are also highlighted.