Cell growth-inhibitory effects of derivatives of antitumor cyclic hexapeptide RA-V obtained from Rubiae radix (V).

Abstract

Alkylehter and ester derivatives of the antitumor cyclic hexapeptide RA-V obtained from the roots of Rubia cordifolia (Rubiaceae) were synthesized and bioassayed for activity against cultured tumor cells. RA-V and its n-hexylether showed significant effects against human nasopharynx carcinoma (KB), P388 lymphocytic leukemia and MM2 mammary carcinoma cells. The activity values (log 1/IC50) of ether derivatives of RA-V gave an upward parabolic or bilinear relationship when plotted against log P (P: partition coefficient determined with the 1-octanol/water system) as the carbon number of the side chain at the phenol moiety of RA-V was increased, the optimum log P values being in the range from 3.5 to 4.9. The ester derivatives showed a similar relationship, the optimum log P values being 6.3-6.7, which is higher than that of the ether derivatives. The lethal effect of RA-V on KB cells was clearly different from that of mitomycin C, and RA-V was concluded to be a "time-dependent drug" like vinblastine.