Selective Anti-proliferative Activity of Indole Alkaloids from Rhazya stricta Decne Leaves

Rhazya stricta is a rich indole alkaloid medicinal plant species, that is used in traditional medicine particularly in Middle East countries to treat inflammations, diabetes, rheumatism, and skin disorders. The alkaloid plant extract of R. stricta was fractionated on aluminum oxide column and further purified by different chromatographic methods. The chemical structures of the isolated compounds were elucidated by interpretation of their 1D and 2D NMR, IR, UV and MS spectral data. The potential antitumor effect was examined against three cancer cell lines; HCT-116-colon cancer, PC-3-prostate cancer and HepG2-liver cancer as well as a control cell line (Vero) using MTT assay. Two new indole alkaloids, identified as 16-epi-stemmadenine-N-oxide (1) and stemmadenine-N-methyl (2), along with the known indole alkaloid 20-epi-antirhine (3) were isolated from the leaves of Rhazya stricta. Compound 2, stemmadenine-N-methyl exhibited a reasonable selectivity index and a broad anticancer effect against the examined cell lines with IC50 35.0±0.7, 35.0±0.6, 40.0±0.7and 79.0±1.0 μM, respectively. Furthermore, the effect of stemmadenine-N-methyl was evaluated on cell migration using woundhealing assay. It significantly hindered cell migration and delayed-wound healing. 16-epistemmadenine- N-oxide and stemmadenine-N-methyl are new indole alkaloids isolated from the leaves of Rhazya stricta, of which stemmadenine-N-methyl selectively inhibited the proliferation of three different cancer cell lines. In addition, it prevented cell migration and delayed wound-healing. Further studies are required to confirm the mechanism by which this promising alkaloid exhibits its antitumor activity.