STUDIES ON RA DERIVATIVES .1. PREPARATION AND CYTOTOXICITY OF CYCLIC HEXAPEPTIDES, RA DERIVATIVES

Several aromatic ring substituent modified RA derivatives were prepare d from RA-VII (1), RA-V (8) and RA-II (11), and evaluated for cytotoxi city against P388 leukemia and KB cells. In terms of IC50 values, the C(zeta) methoxyl group of Tyr-3 greatly influenced the activities, whi le the substituents at the C(zeta) position of Tyr-6 were less importa nt. One of the derivatives, Tyr-C(zeta)-deoxyRA-V (9, P388, IC50, 0.00 25 mug/ml) was nearly as active as RA-VII (1, 0.0013 mug/ml), and also expressed promising anti-P388 in vivo activity (test/control = 171%, at 25 mg/kg).