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(-)-秋水仙碱衍生物的最新研究进展:合成与构效关系。

Recent developments on (-)-colchicine derivatives: Synthesis and structure-activity relationship.

机构信息

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.

出版信息

Eur J Med Chem. 2020 Jan 1;185:111788. doi: 10.1016/j.ejmech.2019.111788. Epub 2019 Oct 18.

Abstract

(-)-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.

摘要

(-)-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。

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