Alkaloids from the Leaves of Antidesma acidum and Their Cytotoxic Activity

Background: Traditional Chinese medicines have attracted increasing interest as potential sources of novel drugs with a wide range of biological and pharmacological activities. The leaves of Antidesma acidum Retz. were used in traditional medicine for treatment of stomachache of children, digestion related issues and diabetes. Moreover, phytochemical investigations of this plant confirmed the presence of alkaloids, triterpenes, and flavonoids. Methods: Using chromatographic methods to isolate compounds from the methanol extract of the leaves of A. acidum. The cytotoxic activities of compounds were evaluated by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, compounds showed significant cytotoxic activity were chosen for further study apoptosis characteristics. Results: Five carbazole alkaloids, clauszoline B (1), clauszoline H (2), mukonal (3), 7-methoxymukonal (4), and heptaphyline (5) and three coumarin derivatives, 5-demethyltoddaculin (6), xanthoxyletin (7), and alloxanthoxyletin (8) were isolated from the leaves of Antidesma acidum. Compounds 1 and 4 exhibited the significant cytotoxic activity on HL-60 with the IC50 values of 4.8 +/- 0.2 and 8.0 +/- 0.9 mu M, respectively. These compounds did not inhibit the growth of HEL-99 normal cell line. The further test indicated compound 1 induced apoptosis via alteration of expression of apoptosis-related proteins and decreased phosphorylation of AKT in HL-60 cells. Conclusion: The results suggested that the constituents from Antidesma acidum may contain effective compounds which can be used as anticancer agents.