Drug Discovery Lab, Department of Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Hong Kong, 999077, Hong Kong SAR.
Laboratory of Medicinal Chemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Avenue 47, 119991, Moscow, Russian Federation.
Chembiochem. 2023 Jun 1;24(11):e202300161. doi: 10.1002/cbic.202300161. Epub 2023 May 3.
Since the discovery of anticancer properties of a naturally occurring hexacyclic marine alkaloid Lamellarin D, the attempts have been made to prepare its synthetic analogues and elucidate the effects of each structural component on their activity profile. While F-ring-free, A-ring-free and B-ring-open lamellarins are known, E-ring-free analogues have never been investigated. In this work, we developed a facile and straightforward synthetic method toward E-ring-free lamellarin analogues based on the [3+2]-cycloaddition. For the first time, we prepared several pentacyclic lamellarin analogues without E-ring in their structure and assessed their cytotoxicity in a panel of cancer cell lines in comparison with several hexacyclic lamellarins. E-ring-free lamellarins were devoid of cytotoxicity due to their poor solubility in cellular environment.
自从发现天然存在的六环海洋生物碱 Lamellarin D 具有抗癌特性以来，人们一直试图制备其合成类似物，并阐明每个结构成分对其活性谱的影响。虽然已经知道 F 环缺失、A 环缺失和 B 环开环的 Lamellarin，但从未研究过 E 环缺失的类似物。在这项工作中，我们基于 [3+2]-环加成开发了一种简便的合成 E 环缺失 Lamellarin 类似物的方法。我们首次制备了几个结构中没有 E 环的五环 Lamellarin 类似物，并将其细胞毒性与几种六环 Lamellarin 进行了比较。由于 E 环缺失的 Lamellarin 在细胞环境中的溶解度较差，因此它们没有细胞毒性。
