Indian Institute of Chemical Technology, Division of Organic Chemistry, Tarnaka, Hyderabad, India.
Expert Opin Investig Drugs. 2012 May;21(5):619-35. doi: 10.1517/13543784.2012.676043.
Benzothiazole scaffold comprises a bicyclic ring system and is known to exhibit a wide range of biological properties including antimicrobial and anticancer activities. Benzothiazole derivatives have long been therapeutically used for the treatment of various diseases. However, in recent years, 2-arylbenzothiazoles have emerged as an important pharmacophore in the development of antitumor agents. The promising biological profile and synthetic accessibility have been attractive in the design and development of new benzothiazoles and their conjugate systems as potential chemotherapeutics.
This review mainly focuses on the structural modifications of benzothiazole scaffold, development of various series of benzothiazoles and their conjugates as new antitumor agents. Furthermore, heterocyclic derivatives bearing benzothiazole moiety and their in vitro as well as in vivo screening, structure-activity relationships (SAR), mechanism, pharmacokinetics, clinical use and their future therapeutic applications are discussed here.
A large number of benzothiazole derivatives discussed here possess potent anticancer activity and can be further developed as drug candidates. Benzothiazole conjugates could also display synergistic effect and still there is a need to use the drug combinations permitting lower dose and development of new generation of drugs. Despite encouraging results that have been observed for their response to tumor in clinical studies, full characterization of their toxicity is further required for their clinical usage as safe drugs for the treatment of cancer. We believe that this review gives a better understanding and scope for future drug design and development of benzothiazole-based compounds to implicate their use in cancer chemotherapy.
苯并噻唑骨架由双环系统组成，已知其具有广泛的生物活性，包括抗菌和抗癌活性。苯并噻唑衍生物长期以来一直被用于治疗各种疾病。然而，近年来，2-芳基苯并噻唑已成为抗肿瘤药物开发中重要的药效团。有希望的生物学特征和合成可及性在设计和开发新的苯并噻唑及其共轭体系作为潜在化疗药物方面具有吸引力。
本文主要集中讨论苯并噻唑骨架的结构修饰、各种系列苯并噻唑及其共轭物作为新型抗肿瘤药物的发展。此外，还讨论了含有苯并噻唑部分的杂环衍生物及其体外和体内筛选、构效关系 (SAR)、机制、药代动力学、临床用途及其未来的治疗应用。
本文讨论的大量苯并噻唑衍生物具有很强的抗癌活性，可以进一步开发为候选药物。苯并噻唑共轭物也可能显示协同作用，仍然需要使用允许降低剂量的药物组合，并开发新一代药物。尽管在临床研究中观察到它们对肿瘤的反应令人鼓舞，但仍需要进一步全面评估其毒性，以确保将其作为安全药物用于癌症治疗。我们相信，这篇综述为基于苯并噻唑的化合物的药物设计和开发提供了更好的理解和前景，以将其用于癌症化疗。
