Chemler Sherry R
The University at Buffalo, The State University of New York, Buffalo, NY 14260, USA.
Curr Bioact Compd. 2009 Mar 1;5(1):2-19. doi: 10.2174/157340709787580928.
The phenanthroindolizidine and phenanthroquinolizidine alkaloids, typified by tylophorine and cryptopleurine, are a family of plant-derived small molecules with significant therapeutic potential. The plant extracts have been used in herbal medicine and the isolated compounds have displayed a range of promising therapeutic activity such as anti-ameobicidal, anti-viral, anti-inflammatory and anti-cancer activity. Despite their therapeutic protential, no compounds in this class have fully passed clinical trials. Drawbacks include low in vivo anti-cancer activity, central nervous system toxicity and low natural availability. A number of biological effects of these compounds, such as protein and nucleic acid synthesis suppression, have been identified, but the specific biomolecular targets have not yet been identified. Significant effort has been expended in the synthesis and structure-activity-relationship (SAR) studies of these compounds with the hope that a new drug will emerge. This review will highlight important contributions to the isolation, synthesis, SAR and mechanism of action of the phenanthroindolizidine and pheanthroquinolizidine alkaloids.
以娃儿藤碱和隐肋马钱子碱为代表的菲并吲哚里西啶和菲并喹诺里西啶生物碱，是一类具有重要治疗潜力的植物源小分子。植物提取物已被用于草药，分离出的化合物已显示出一系列有前景的治疗活性，如抗阿米巴、抗病毒、抗炎和抗癌活性。尽管它们具有治疗潜力，但该类化合物中没有一种完全通过临床试验。缺点包括体内抗癌活性低、中枢神经系统毒性和天然可得性低。这些化合物的一些生物学效应，如蛋白质和核酸合成抑制，已被确定，但具体的生物分子靶点尚未确定。人们在这些化合物的合成和构效关系（SAR）研究方面投入了大量精力，希望能开发出一种新药。本综述将重点介绍菲并吲哚里西啶和菲并喹诺里西啶生物碱在分离、合成、SAR及作用机制方面的重要贡献。
