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  • Title: Preparation and cytotoxicity of cyclic hexapeptides, RA derivatives.
    Author: Itokawa H, Kondo K, Hitotsuyanagi Y, Nakamura A, Morita H, Takeya K.
    Journal: Chem Pharm Bull (Tokyo); 1993 Jul; 41(7):1266-9. PubMed ID: 8374996.
    Abstract:
    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).
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