ANTINEOPLASTIC AGENTS 397 - ISOLATION AND STRUCTURE OF SESTERSTATIN-4AND SESTERSTATIN-5 FROM HYRTIOS-ERECTA (THE REPUBLIC OF MALDIVES)

The wide ranging marine sponge Hyrtios erecta is the source of the spo ngistatins, a new class of macrocyclic lactone antineoplastic agents. Continuation of a detailed investigation of cancer cell growth inhibit ory (P388 lymphocytic leukemia) fractions (trace) from H. erecta has r evealed the presence (10(-5) to 10(-7)% yield) of cytotoxic pentacycli c sesterterpenes. Employing P388 leukamia and human tumor cell line-gu ided bioassay techniques, two new moderate inhibitors of cancer cells were isolated and named sesterstatins 4 (Ia, P388 ED50 4.9 mu g/mL) an d 5 (1b, DU-145 prostate GI(50) 1.9 mu g/mL). Similar to other sestert erpenes, sesterstatin 5 inhibited growth of a Gram-positive bacterium. High field (500 MHz) 2-D NMR techniques were primarily employed for i nitial structural assignments, and structural assignments were confirm ed by X-ray crystal structure determination of sesterstatin 4 (1a) and 5 (1b). (C) 1998 Elsevier Science Ltd. All rights reserved.