Bailly Christian
Pierre Fabre Research Institute, Research & Development Center, 3 Avenue Hubert Curien, BP 13562, 31035 Toulouse cedex 1, France.
Mar Drugs. 2015 Feb 19;13(3):1105-23. doi: 10.3390/md13031105.
In 1985 the first lamellarins were isolated from a small oceanic sea snail. Today, more than 50 lamellarins have been inventoried and numerous derivatives synthesized and tested as antiviral or anticancer agents. The lead compound in the family is lamellarin D, characterized as a potent inhibitor of both nuclear and mitochondrial topoisomerase I but also capable of directly interfering with mitochondria to trigger cancer cell death. The pharmacology and chemistry of lamellarins are discussed here and the mechanistic portrait of lamellarin D is detailed. Lamellarins frequently serve as a starting point in the design of anticancer compounds. Extensive efforts have been devoted to create novel structures as well as to improve synthetic methods, leading to lamellarins and related pyrrole-derived marine alkaloids.
1985年,首批片螺素从一种小型海洋蜗牛中分离出来。如今,已鉴定出50多种片螺素,并合成和测试了众多衍生物作为抗病毒或抗癌药物。该家族中的先导化合物是片螺素D,它被表征为细胞核和线粒体拓扑异构酶I的有效抑制剂,但也能够直接干扰线粒体以触发癌细胞死亡。本文讨论了片螺素的药理学和化学性质,并详细阐述了片螺素D的作用机制。片螺素经常作为抗癌化合物设计的起点。人们付出了巨大努力来创造新结构并改进合成方法,从而得到了片螺素及相关的吡咯衍生海洋生物碱。