2-Aminobenzothiazoles in anticancer drug design and discovery.
2-Aminobenzothiazoles in anticancer drug design and discovery.
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DOI：
10.1016/j.bioorg.2023.106477
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发表时间：
2023-03
影响因子：
5.1
通讯作者：
Guang Huang;T. Cierpicki;J. Grembecka
中科院分区：
文献类型：
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作者：
Guang Huang;T. Cierpicki;J. Grembecka
癌症是世界范围内死亡和发病的主要原因之一。人们进行了大量的研究工作，以开发具有更高抗癌功效的新化学实体。2-氨基苯并噻唑是一类重要的含一个硫和两个氮原子的杂环化合物，具有广泛的医学和药理活性，包括抗肿瘤、抗细菌、抗疟疾、抗炎和抗病毒活性。近年来，大量高效低毒的2-氨基苯并噻唑类化合物被发现作为新的抗癌药物。在此，我们根据它们对肿瘤相关蛋白的活性，对这类化合物进行了全面的综述，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、bclxl、HSP90、突变的p53蛋白、DNA拓扑异构酶、HDAC、NSD1、LSD1、FTO、mPGES-1、SCD、HCA IX/XII和CXCR。此外，本文还介绍了2-氨基苯并噻唑衍生物及其金属络合物的抗癌潜力。此外，本文还对2-氨基苯并噻唑类新抗癌药物的设计策略、作用机制、构效关系以及临床前开发的更高级阶段进行了广泛的综述。最后，举例说明了2-氨基苯并噻唑与其他杂环化合物相比具有的优势。
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-XL, 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.