Isolation and structure of the cell growth inhibitory constituents from the western Pacific marine sponge Axinella sp

• Published in: Journal of medicinal chemistry 1991-11, Vol.34 (11), p.3339-3340
• Main Authors: Pettit, G R, Herald, C L, Boyd, M R, Leet, J E, Dufresne, C, Doubek, D L, Schmidt, J M, Cerny, R L, Hooper, J N, Rützler, K C
• Format: Article
• Language: English
• Subjects: Alkaloids - isolation & purification; Alkaloids - therapeutic use; Animals; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - therapeutic use; Axinella; Ethers, Cyclic - isolation & purification; Ethers, Cyclic - therapeutic use; Leukemia P388 - drug therapy; Macrolides; Marine; Peptides, Cyclic - isolation & purification; Peptides, Cyclic - therapeutic use; Porifera; Porifera - chemistry
• ISSN: 0022-2623
• DOI: 10.1021/jm00115a027

While isolation of alkaloids from marine Porifera has been accelerating, only a small number of antineoplastic or peptide constituents have been recovered from these invertebrates. Our isolation and structural determination of the P388 lymphocytic leukemia (PS system) cell growth inhibitory cyclooctapeptide hymenistatin 1 from a Palau sponge in the genus Hymeniacidon represented the first such combination of source, structural type, and biological activity. We have also found an Axinella sp. (Demospongiae class) collected (in 1979) in Palau (at -40 m) to yield a methylene chloride-2-propanol extract that provided a 101% increase in life span (at 100 mg/kg) against the PS leukemia with ED sub(50) 2.5 mu g/mL in the corresponding cell line. The most potent in vivo components were established as the polyether macrolides, homohalichondrin B and halichondrin B.