Antiproliferative homoscalarane sesterterpenes from two Madagascan sponges

• Published in: Bioorganic & medicinal chemistry Vol. 21; no. 11; pp. 2912 - 2917
• Main Authors: Harinantenaina, Liva, Brodie, Peggy J., Maharavo, Jean, Bakary, Gisele, TenDyke, Karen, Shen, Yongchun, Kingston, David G.I.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.06.2013; Elsevier
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; Antiproliferative activity; Biochemistry & Molecular Biology; Cancer; Carteriospongia; Cell Line, Tumor; Cell Proliferation - drug effects; Chemistry; Chemistry, Medicinal; Chemistry, Organic; ethyl acetate; Homoscalarane; Humans; Inhibitory Concentration 50; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; Marine natural products; melanoma; Molecular Structure; Nuclear magnetic resonance; nuclear magnetic resonance spectroscopy; Pharmacology & Pharmacy; Physical Sciences; Porifera - chemistry; Science & Technology; Sesterterpenes; Sesterterpenes - chemistry; Sesterterpenes - isolation & purification; Sesterterpenes - pharmacology; Sponge; Structure-Activity Relationship; OGLFTTHUASEWEH-TYBNXFRGSA-N; Antiproliferative activity; Marine natural products; ICZJCUYQFKPVHU-IMRWOHAXSA-N; Sponge; SCQWNYQIOKUMKH-AODGPMNPSA-N; Nuclear magnetic resonance; Carteriospongia; Homoscalarane; Sesterterpenes; OGLFTTHUASEWEH-CXBFZGAFSA-N; PHYLLOSPONGIA-FOLIASCENS; BISHOMOSCALARANE SESTERTERPENES
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2013.03.078

Dereplication of the antiproliferative ethyl acetate fraction of the Madagascan sponge Carteriospongia sp. led to the detection and isolation of the two known homoscalarane-type sesterterpenes 1 and 2. Investigation of a similar sponge containing closely related compounds afforded the four new antiproliferative homoscalarane sesterterpenes (3 and 5−7). The structures of all isolated compounds were elucidated by spectroscopic methods, including UV, IR and 1D and 2D NMR. Compounds 1, 3 and 5 displayed submicromolar antiproliferative activity against the A2780 ovarian cell line with IC50 values of 0.65, 0.26 and 0.28μM, respectively, while compounds 6 and 7 showed moderate activity (4.5 and 8.7μM, respectively). Compounds 3 and 5 also displayed anti-proliferative activity against the H522-T1 non-small cell lung and A2058 human melanoma cancer cell lines.