苯并噻唑是一类杂环,具有多种抗癌用途,抗生素,抗病毒,和抗炎药。苯并噻唑是用于调节多种生物学功能的药物发现程序中的特权支架。本文就针对低氧肿瘤的新型苯并噻唑衍生物的设计与合成作一综述。癌症是一个主要的健康问题,是导致死亡的主要原因之一。肿瘤缺氧区域促进增殖,恶性肿瘤,和对药物治疗的抗药性,导致涉及血管内皮生长因子等药物靶标的关键信号通路失调,表皮生长因子受体,肝细胞生长因子受体,双特异性蛋白激酶,细胞周期蛋白依赖性蛋白激酶,酪蛋白激酶2,Rho相关卷曲形成蛋白激酶,间膜内皮细胞激酶,环加氧酶-2,腺苷激酶,溶血磷脂酸酰基转移酶,硬脂酰辅酶A去饱和酶,过氧化物酶体增殖物激活受体,硫氧还蛋白,热休克蛋白,和碳酸酐酶IX/XII。反过来,它们调节血管生成,扩散,分化,和细胞存活,控制细胞周期,炎症,免疫系统,和代谢改变。在过去的几年中,据报道有各种各样的苯并噻唑干扰参与肿瘤发生的各种蛋白质,更具体地说,在缺氧肿瘤中。由于低氧诱导因子激活级联反应,许多低氧靶标过表达,并且可能不存在于正常组织中。提供了选择性靶向低氧癌症的潜在策略。
Benzothiazoles are a class of heterocycles with multiple applications as anticancer, antibiotic, antiviral, and anti-inflammatory agents. Benzothiazole is a privileged scaffold in drug discovery programs for modulating a variety of biological functions. This review focuses on the design and synthesis of new benzothiazole derivatives targeting hypoxic tumors. Cancer is a major health problem, being among the leading causes of death. Tumor-hypoxic areas promote proliferation, malignancy, and resistance to drug treatment, leading to the dysregulation of key signaling pathways that involve drug targets such as vascular endothelial growth factor, epidermal growth factor receptor, hepatocyte growth factor receptor, dual-specificity protein kinase, cyclin-dependent protein kinases, casein kinase 2, Rho-related coil formation protein kinase, tunica interna endothelial cell kinase, cyclooxygenase-2, adenosine kinase, lysophosphatidic acid acyltransferases, stearoyl-CoA desaturase, peroxisome proliferator-activated receptors, thioredoxin, heat shock proteins, and carbonic anhydrase IX/XII. In turn, they regulate angiogenesis, proliferation, differentiation, and cell survival, controlling the cell cycle, inflammation, the immune system, and metabolic alterations. A wide diversity of benzothiazoles were reported over the last years to interfere with various proteins involved in tumorigenesis and, more specifically, in hypoxic tumors. Many hypoxic targets are overexpressed as a result of the hypoxia-inducible factor activation cascade and may not be present in normal tissues, providing a potential strategy for selectively targeting hypoxic cancers.