Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Bioorg Chem. 2023 Jun;135:106477. doi: 10.1016/j.bioorg.2023.106477. Epub 2023 Mar 20.
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, 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.
癌症是全球主要的死亡和发病原因之一。为了开发具有更好抗癌疗效的新化学实体，已经进行了大量的研究工作。2-氨基苯并噻唑是一种含有一个硫原子和两个氮原子的重要杂环类，与广泛的医学和药理学活性有关，包括抗肿瘤、抗菌、抗疟、抗炎和抗病毒活性。近年来，发现了大量具有高活性和低毒性的 2-氨基苯并噻唑化合物，作为新型抗癌药物。本文综述了该类化合物基于其对肿瘤相关蛋白的活性，包括酪氨酸激酶（CSF1R、EGFR、VEGFR-2、FAK 和 MET）、丝氨酸/苏氨酸激酶（Aurora、CDK、CK、RAF 和 DYRK2）、PI3K 激酶、BCL-X、HSP90、突变型 p53 蛋白、DNA 拓扑异构酶、HDAC、NSD1、LSD1、FTO、mPGES-1、SCD、hCA IX/XII 和 CXCR。此外，本文还描述了 2-氨基苯并噻唑衍生的螯合剂和金属配合物的抗癌潜力。此外，本文还广泛综述了 2-氨基苯并噻唑作为新型抗癌药物的设计策略、作用机制、构效关系（SAR）和更先进的临床前开发阶段。最后，还强调了 2-氨基苯并噻唑相对于其他杂环系统的优势。
