STDIES ON ANTITUMOR AGENTS FROM HIGHER PLANTS

制癌作用

To data, many types of compounds having antineoplastic activity have been isolated from higher plants, that is, alkalodids, terpenes, lignans, steroids and so on. Some of ther were isolated from Indonesian plants, Curcuma xanthorrhiza and Eurycoma longifolia. Bisaborane type compounds were compounds were isolated as antimeoplastic compounds againest Sarcoma 180A from C. xanthorrhiza, and quassinoids and euryrene type triterpenes from triterpenes from El longifolia. Casearines, a kind of diterpene, had been isolated as cytotxic components from Casearia sylvestris distributed in South America. RA series Cyclic hexapeptides isolated from Rubia akane and R. cordifolia also have strong antineoplastic activity against various types of tumors. Till now, 16 kinds of RA series compounds were isolated and named as RA-I~XVI. Moreover, monoglucoside of RA-V newly isolated from same plant. Many kinds of derivatives including natural RA compounds were tested for QSAR, and one of them, RA-VII was screened up as a most suitable substance as an antitumor agent. RA-VII(=RA 700) has strong cytotoxic activity against KB cells, P388 lymphocytic leukemia and MM2 mammary carcinoma cells. In some solution, three conformers of RA-VII were observed by NMR. It was discussed the relationship between conformation and activity. Total synthesis was already completed, but there is left room for improvement. Phase I clinical trials for RA-VII has been finished, then Phase II trials will be started before long.