Univ Coimbra, FFUC, Laboratory of Pharmaceutical Chemistry, Azinhaga de Santa Comba, Pólo III - Pólo das Ciências da Saúde, 3000-548, Coimbra, Portugal.
Univ Coimbra, CIEPQPF, FFUC, Laboratory of Pharmaceutical Chemistry, Azinhaga de Santa Comba, Pólo III - Pólo das Ciências da Saúde, 3000-548, Coimbra, Portugal.
Eur J Med Chem. 2020 Sep 1;201:112327. doi: 10.1016/j.ejmech.2020.112327. Epub 2020 May 5.
Functional group modification is one of the main strategies used in drug discovery and development. Despite the controversy of being identified for many years as a biologically hazardous functional group, the introduction of an epoxide function in a structural backbone is still one of the possible modifications being implemented in drug design. In this manner, it is our intention to prove with this work that epoxides can have significant interest in medicinal chemistry, not only as anticancer agents, but also as important drugs for other pathologies. Thus, this revision paper aims to highlight the biological activity and the proposed mechanisms of action of several epoxide-containing molecules either in preclinical studies or in clinical development or even in clinical use. An overview of the chemistry of epoxides is also reported. Some of the conclusions are that effectively most of the epoxide-containing molecules referred in this work were being studied or are in the market as anticancer drugs. However, some of them in preclinical studies, were also associated with other different activities such as anti-malarial, anti-arthritic, insecticidal, antithrombotic, and selective inhibitory activity of FXIII-A (a transglutaminase). As for the epoxide-containing molecules in clinical trials, some of them are being tested for obesity and schizophrenia. Finally, drugs containing epoxide groups already in the market are mostly used for the treatment of different types of cancer, such as breast cancer and multiple myeloma. Other diseases for which the referred drugs are being used include heart failure, infections and gastrointestinal disturbs. In summary, epoxides can be a suitable option in drug design, particularly in the design of anticancer agents, and deserve to be better explored. However, and despite the promising results, it is imperative to explore the mechanisms of action of these compounds in order to have a better picture of their efficiency and safety.
功能基团修饰是药物发现和开发中使用的主要策略之一。尽管多年来一直被认为是具有生物危害性的功能基团，但在结构骨架中引入环氧化物官能团仍然是药物设计中可能进行的修改之一。通过这种方式，我们旨在通过这项工作证明环氧化物在药物化学中具有重要的意义，不仅作为抗癌剂，而且作为其他病理学的重要药物。因此，本文旨在强调含有环氧化物的几种分子的生物学活性和提出的作用机制，无论是在临床前研究、临床开发中，还是在临床应用中。还报告了环氧化物化学的概述。一些结论是，实际上，在这项工作中提到的大多数含有环氧化物的分子都被用作抗癌药物进行研究或已经在市场上。然而，其中一些在临床前研究中，也与其他不同的活性相关，如抗疟疾、抗关节炎、杀虫、抗血栓形成和 FXIII-A（转谷氨酰胺酶）的选择性抑制活性。对于临床试验中的含环氧化物分子，其中一些正在测试用于肥胖症和精神分裂症。最后，已经在市场上的含环氧化物的药物主要用于治疗不同类型的癌症，如乳腺癌和多发性骨髓瘤。这些药物还用于治疗其他疾病，包括心力衰竭、感染和胃肠道紊乱。总之，环氧化物可以成为药物设计的一个合适选择，特别是在抗癌剂的设计中，值得进一步探索。然而，尽管有很有前景的结果，但必须探索这些化合物的作用机制，以便更好地了解它们的效率和安全性。
