ABSTRACT
A new dimeric indole alkaloid, vincazalidine A consisting of an aspidosperma type and a modified iboga type with 1-azatricyclo ring system consisting of one azepane and two piperidine rings coupled with an oxazolidine ring was isolated from Catharanthus roseus, and the structure including absolute stereochemistry was elucidated on the basis of spectroscopic data as well as DP4 statistical analysis. Vincazalidine A induced G2 arrest and subsequent apoptosis in human lung carcinoma cell line, A549 cells.
Subject(s)
Alkaloids , Antineoplastic Agents , Aspidosperma , Catharanthus , Humans , Catharanthus/chemistry , Catharanthus/metabolism , Indole Alkaloids/pharmacology , Indole Alkaloids/chemistry , Aspidosperma/chemistry , Aspidosperma/metabolismABSTRACT
A dimeric indole alkaloid, isovincathicine consisting of an aspidosperma type and modified iboga with C-7-C-20 connection type skeletons was first isolated from Catharanthus roseus, and the structure including stereochemistry was elucidated on the basis of spectroscopic data as well as DP4 statistical analysis. Isovincathicine inhibited cell proliferation in A549 cells. We investigated the detailed mode of action of isovincathicine-induced inhibitory effects on cell proliferation in A549 cells. Flow cytometric analysis showed that isovincathicine-treated cells accumulated in the G2 phase after 24 h, and the percentage of cells showing cell death increased after 48 h. Western blotting also showed increased expression of BimEL, an apoptosis-related protein, and decreased expression of Mcl-1 and Bcl-xL. Isovincathicine was suggested to induce apoptosis in A549 cells by a mechanism is similar to that of vinblastine.