sesterstatin-5 and Leukemia-P388

A new scalarane-type pentacyclic sesterterpene, sesterstatin 6 (6), was isolated in 8.3 x 10(-7)% yield from the Republic of Maldives marine sponge Hyrtios erecta. The structure was elucidated by analyses of HRMS and high-field 2-D NMR spectra. Sesterstatin 6 showed significant cancer cell growth inhibition against murine P388 lymphocytic leukemia and a series of human tumor cell lines (ED50 0.17 microg/mL, GI50 1.8-8.9 x 10(-1) microg/mL) and proved to be the most inhibitory of the series.

Topics: Animals; Antineoplastic Agents; Drug Screening Assays, Antitumor; Humans; Indian Ocean; Leukemia P388; Mice; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Porifera; Terpenes; Tumor Cells, Cultured

The wide ranging marine sponge Hyrtios erecta is the source of the spongistatins, a new class of macrocyclic lactone antineoplastic agents. Continuation of a detailed investigation of cancer cell growth inhibitory (P388 lymphocytic leukemia) fractions (trace) from H. erecta has revealed the presence (10(-5) to 10(-7)% yield) of cytotoxic pentacyclic sesterterpenes. Employing P388 leukemia and human tumor cell line-guided bioassay techniques, two new moderate inhibitors of cancer cells were isolated and named sesterstatins 4 (1a, P388 ED50 4.9 micrograms/mL) and 5 (1b, DU-145 prostate GI50 1.9 micrograms/mL). Similar to other sesterterpenes, sesterstatin 5 inhibited growth of a Gram-positive bacterium. High field (500 MHz) 2-D NMR techniques were primarily employed for initial structural assignments, and structural assignments were confirmed by X-ray crystal structure determination of sesterstatin 4 (1a) and 5 (1b).

Topics: Animals; Anti-Bacterial Agents; Antineoplastic Agents; Cell Division; Cell Survival; Gram-Positive Bacteria; Humans; Indian Ocean Islands; Leukemia P388; Male; Mice; Microbial Sensitivity Tests; Models, Molecular; Molecular Conformation; Molecular Structure; Porifera; Structure-Activity Relationship; Terpenes; Tumor Cells, Cultured