1. Epoxide containing molecules: A good or a bad drug design approach
Ana R Gomes, Carla L Varela, Elisiário J Tavares-da-Silva, Fernanda M F Roleira 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.
2. Ring opening of epoxides with C-nucleophiles
Sadia Faiz, Ameer Fawad Zahoor Mol Divers. 2016 Nov;20(4):969-987. doi: 10.1007/s11030-016-9686-7. Epub 2016 Jul 4.
Ring opening of epoxides has been an area of interest for organic chemists, owing to their reactivity toward nucleophiles. Such reactions yield important products depending on the type of nucleophiles used. This review article covers the synthetic approaches (1991-2015) used for the ring opening of epoxides via carbon nucleophiles.
3. Epoxides: Developability as active pharmaceutical ingredients and biochemical probes
Baljit Kaur, Palwinder Singh Bioorg Chem. 2022 Aug;125:105862. doi: 10.1016/j.bioorg.2022.105862. Epub 2022 May 11.
Epoxide functional group is a part of several natural as well as synthetic compounds. Irrespective of the role of epoxide group in drug efficacy and the use of epoxide compounds as tool molecules, uncertainty prevails over concerns associated with the reactivity of this functional group. Herein, we compile information about epoxide-based medicinal compounds and biochemical probes and look into the related advantages and challenges of the epoxide functional group. As a whole, this study is focussed on analyzing the strategies which have been adopted for the successful development of epoxide-based compounds within drug discovery programs.
