Preparation and Cytotoxicity of Cyclic Hexapeptides, RA Derivatives

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_ζ methoxyl group of Tyr-3 greatly influenced the activities, while the substituents at the C_ζ position of Tyr-6 were less important. One of the derivatives, Tyr-6-C_ζ-deoxyRA-V (9, P388, IC₅₀, 0.0025μg/ml) was nearly as active as RA-VII (1, 0.0013μg/ml), and also expressed promising anti-P388 in vivo activity (test/control=171%, at 25mg/kg).