Faculty of Industrial Sciences & Technology, Universiti Malaysia Pahang, Gambang, 26300, Kuantan, Pahang, Malaysia.
Chemistry Programme, School of Chemical Sciences and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600, Bangi, Selangor, Malaysia.
Eur J Med Chem. 2020 Jan 1;185:111788. doi: 10.1016/j.ejmech.2019.111788. Epub 2019 Oct 18.
(-)-Colchicine, an anti-microtubulin polymerization agent, is a valuable medication and the drug of choice for gout, Behçet's disease and familial Mediterranean fever. It has a narrow therapeutic index due to its high toxicity towards normal cells. Nonetheless, numerous (-)-colchicine derivatives have been synthesized and studied for their structure-activity relationship and preferential toxicity. Different functional groups such as amides, thioamides, N-arylurea and 8,12-diene cyclic have been incorporated into (-)-colchicine, resulting in derivatives (with moieties) that include electron-withdrawing and electron-donating groups. This review article focuses on recent developments in the chemical synthesis of (-)-colchicine derivatives, the substituents used, the functional groups linked to the substituents, the moieties and biological studies. Moreover, the current classification of derivatives based on the (-)-colchicine rings, namely ring A, B, and C (-)-colchicine derivatives, is discussed. This work demonstrates and summarizes the significance of (-)-colchicine derivatives in the biological field, and discusses their promising therapeutics for the future.
(-)-秋水仙碱,一种抗微管聚合剂,是一种有价值的药物,是痛风、贝切特病和家族性地中海热的首选药物。由于其对正常细胞的高毒性,它的治疗指数很窄。尽管如此,已经合成了许多(-)-秋水仙碱衍生物,并对其结构-活性关系和选择性毒性进行了研究。不同的官能团,如酰胺、硫代酰胺、N-芳基脲和 8,12-二烯环,已被引入(-)-秋水仙碱中,导致包含吸电子和供电子基团的衍生物(带有取代基)。本文重点介绍了(-)-秋水仙碱衍生物的化学合成、取代基、与取代基相连的官能团、取代基和生物研究方面的最新进展。此外,还讨论了基于(-)-秋水仙碱环的衍生物的当前分类,即 A、B 和 C 环(-)-秋水仙碱衍生物。这项工作展示并总结了(-)-秋水仙碱衍生物在生物学领域的重要性,并讨论了它们在未来有希望的治疗方法。