Antineoplastic agents 397: Isolation and structure of sesterstatins 4 and 5 from hyrtios erecta (the republic of maldives)

• Published in: Bioorganic & medicinal chemistry letters Vol. 8; no. 16; pp. 2093 - 2098
• Main Authors: Pettit, George R., Tan, Rui, Melody, Noeleen, Cichacz, Zbigniew A., Herald, Delbert L., Hoard, Michael S., Pettit, Robin K., Chapuis, Jean-Charles
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 18-08-1998; Elsevier
• Subjects: Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - isolation & purification; Anti-Bacterial Agents - pharmacology; Antineoplastic Agents - chemistry; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - toxicity; Biological and medical sciences; Cell Division - drug effects; Cell Survival - drug effects; General pharmacology; Gram-Positive Bacteria - drug effects; Humans; Indian Ocean Islands; Leukemia P388; Male; Medical sciences; Mice; Microbial Sensitivity Tests; Models, Molecular; Molecular Conformation; Molecular Structure; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Porifera; Structure-Activity Relationship; Terpenes - chemistry; Terpenes - isolation & purification; Terpenes - toxicity; Tumor Cells, Cultured; Indian Ocean Islands; Maldive Islands; Antineoplastic agent; Pentacyclic compound; P388-Leukemia; Cytotoxicity; Oxygen heterocycle; Marine environment; Gram positive bacteria; Established cell line; Bacteria; Micrococcales; Micrococcaceae; Tumor cell; Human; Terpenoid; Pharmacognosy; Animal origin; In vitro; Micrococcus luteus; Biological activity; Porifera; Isolation; Invertebrata; Antibacterial agent; Sesterterpenes; Structural analysis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(98)00373-4

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 ED
50 4.9 μg/mL) and 5 (
1b, DU-145 prostate
GI
50 1.9 μg/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).