Preparation and cytotoxicity of cyclic hexapeptides, RA derivatives.
Several aromatic ring substituent modified RA derivatives were prepared from RA-VII (1), RA-V (8) and RA-II (11), and evaluated for cytotoxicity against P388 leukemia and KB cells. In terms of IC50 values, the C zeta methoxyl group of Tyr-3 greatly influenced the activities, while the substituents at the C zeta position of Tyr-6 were less important. One of the derivatives, Tyr-6-C zeta-deoxyRA-V (9, P388, IC50, 0.0025 micrograms/ml) was nearly as active as RA-VII (1, 0.0013 micrograms/ml), and also expressed promising anti-P388 in vivo activity (test/control = 171%, at 25 mg/kg).
Tokyo College of Pharmacy, Japan.
H
H
Itokawa
K
K
Kondo
Y
Y
Hitotsuyanagi
A
A
Nakamura
H
H
Morita
K
K
Takeya
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D007624:KB Cells; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D008815:Mice, Inbred Strains; D010456:Peptides, Cyclic / Q000302:isolation & purification* / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D010456:Peptides, Cyclic; C043548:RA VII