Cell growth-inhibitory effects of derivatives of antitumor cyclic hexapeptide RA-V obtained from Rubiae radix (V).
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.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D007941:Leukemia P388 / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000473:pathology; D051379:Mice; D009062:Mouth Neoplasms; D009303:Nasopharyngeal Neoplasms; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000633:toxicity; D010946:Plants, Medicinal; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; C043547:RA V; C043548:RA VII