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.

• Authors: H Itokawa, K Takeya, N Mori, M Takanashi, H Yamamoto, T Sonobe, S Kidokoro
• Journal: Gan (Gan) Vol. 75 Issue 10 Pg. 929-36 (Oct 1984) ISSN: 0016-450X [Print] Japan
• PMID: 6510638 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antineoplastic Agents
• Peptides, Cyclic
• RA V
• RA VII

Topics

• Animals
• Antineoplastic Agents (chemical synthesis)
• Cell Division (drug effects)
• Cell Line
• Cell Survival (drug effects)
• Humans
• Kinetics
• Leukemia P388 (pathology)
• Mammary Neoplasms, Experimental (pathology)
• Mice
• Mouth Neoplasms
• Nasopharyngeal Neoplasms
• Peptides, Cyclic (chemical synthesis, toxicity)
• Plants, Medicinal
• Structure-Activity Relationship