云南特有假柴龙树属植物中单萜吲哚生物碱及抗肿瘤活性研究

The antitumor drug encounter serious challenges for resistance and selectivity at present. New active molecules for druggability are more urgent. Plant constituents is one of important resources of drugs so far. Monoterpenoid indole alkaloids (MIAs) show high druggability, complicated structure and diverse bioactivities, becoming a research hotspot. .Speceis of Nothapodytes of family Icacinaceae are rich of MIAs, and two of them, N. foetida and N. pittosporoides are important resources of anticancer drug camptothecin. Previous research discovered a serial of alkaloids including 3 new ones. Two new alkaloids, 7-methoxy-camptothecin and 9-methoxy-17-hydroxymappicine exhibited more excellent cytotoxicity to TCA cells than 10-hydroxy-camptothecin and 9-methoxy-camptothecin. However, nearly no alkaloids from Yunnan endemic Nothapodytes plants, N. obscura, N. tomentosa and N. collina are reported to date. This project will concentrate on alkaloidal compositions and their cytotoxicity from above plants, enriching structural diversity of alkaloids and new anticancer candidates. These will benefit for utilization of Nothapodytes resources.

当前抗肿瘤药物面临着耐药性和选择性的重大挑战，加强新药实体分子研发是当务之急。植物化学成分一直是药物的重要来源，其中单萜吲哚生物碱在植物源天然产物中具有高成药率、结构类型丰富、活性多样性等特点，是天然药物化学研究的热点。.茶茱萸科假柴龙树属Nothapodytes植物富含单萜吲哚生物碱，该属植物臭假柴龙树和马比木是抗肿瘤药物喜树碱的重要来源，前期从马比木中发现一系列生物碱，3个新生物碱中7-甲氧基喜树碱和9-甲氧基-17-羟基马比木碱具有显著肿瘤细胞毒活性，前者对人口腔癌细胞增殖抑制率略优于药物10-羟基喜树碱、9-甲氧基喜树碱；但是云南特有的同属植物薄叶假柴龙树、毛假柴龙树、厚叶假柴龙树尚未有生物碱成分研究的报道。本项目将研究这3种植物生物碱成分及抗肿瘤活性，既丰富生物碱结构多样性也期望发现新的活性分子，为假柴龙树属资源利用提供依据。