Long-chain acetylenic ketones from the micronesian sponge haliclona sp. Importance of the 1-yn-3-ol group for antitumor activity

Marine Drugs

Volumn 1, Issue 1, 2003, Pages 46-53

  Zhou, Guang Xiong ^a   Molinski, Tadeusz F ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Cytotoxic activity; Ene yne; HCT 116; Pellynol; Polyacetylene; Porifera

Indexed keywords

EID: 2042512178     PISSN: None     EISSN: 16603397     Source Type: Journal    
DOI: 10.3390/md101046     Document Type: Article

References (15)

1. For examples, see (a) Quinoa, E.; Crews, P. Melynes, polyacetylene constituents from a Vanuatu marine sponge. Tetrahedron Lett. 1988, 29 (17), 2037-2040; (b) Youssef, D. T. A.; Yoshida, W.Y.; Kelly, M.; Scheuer, P. J. New cytotoxic polyacetylenes from a Red Sea sponge Callyspongia species. J. Nat. Prod. 2000, 63, 1406-1410; (c) Guo, Y.; Gavagnin, M.; Trivellone, E.; Cimino, G. Further structural studies on the Petroformynes. J. Nat. Prod. 1995, 58 (5), 712-722.
2. Kim, D.-K.; Lee, M.-Y.; Lee, H. S.; Lee, D. S.; Lee, J.-R.; Lee, B.-J.; Jung, J. H. Polyacetylenes from a marine sponge Petrosia sp. inhibit DNA replication at the level of initiation. Cancer Lett. 2002, 185 (1), 95-101.
3. Kobayashi, M.; Kawazoe, K.; Okamoto, T.; Sasaki, T.; Kitagawa, I. Chem. Pharm. Bull. 1994, 42, 19.
4. For example, pellynols A-D: (a) Fu, X.; Abbas, S. A.; Schmitz, F. J.; Vidavsky, I.; Gross, M. L.; Laney, M.; Schatzmann, R. C.; Cabuslay, R. D. New acetylenic metabolites from the marine sponge Pellina triangulata. Tetrahedron 1997, 53, 799-814; Pellynols E-H were isolated from Theonella sp.; (b) Fu, X.; Schmitz, F. J.; Kelly, M. Swinholides and new acetylenic compounds from an undescribed species of Theonella Sponge. J. Nat. Prod. 1999, 62, 1336-1338, while pellynol I was reported from a South African Pellina sp.; (c) Rashid, M.; Gustafson, K. R.; Boyd, M. R. Pellynol I, a new cytotoxic polyacetylene from the sponge Pellina sp. Nat. Prod. Lett. 2000, 14 (5), 287-392.
5. Dai, J-R.; Hallock, Y. F.; Cardellina III, J. H.; Gray, G. N.; Boyd, M. R. Triangulynes A-H and triangulynic acid, new cytotoxic polyacetylenes from the marine sponge Pellina triangulate. J. Nat. Prod. 1996, 59, 860-866.
6. Nomenclature considerations define the primary alcohol in pellynol A (5) at C1 and the terminal acetylene carbon at C33. Systematic numbering of the corresponding ketones 1 and 2 would require reversed ordering of locant numbers. In order to emphasis the importance of the terminal propargylic alcohol and retain a useful reference point, we use the terms ‘1-yn-3-ol’ and ‘1-yn-3-one’ to refer to functionality numbered from the ω-terminus with respect to pellynol numbering.
7. Compounds 2, 3, and 4 were not tested against HCT-116 due to insufficient material or decomposition.
8. None of the compounds showed significant antifungal activity (Candida glabrata) in their pure states.
9. This is surprising as other compounds in this class, such as 3-9, exhibit cytotoxicity to mammalian cells.
10. (a) Aoki, S.; Matsui K. Tanaka K. Satari R. Kobayashi M. Lembehyne A, a novel neuritogenic polyacetylene, from a marine sponge of Haliclona sp. Tetrahedron 2002, 56 (51), 9945-9948. (b) Aoki S. Matsui K. Wei H. Murakami N. Kobayashi M. Structure-activity relationship of neuritogenic spongean acetylene alcohols, lembehynes. Tetrahedron 2002, 58 (27), 5417-5422 (c) Aoki S. Matsui K. Takata T. Hong W. Kobayashi M. Lembehyne A, a spongean polyacetylene, induces neuronal differentiation in neuroblastoma cell. Biochem. Biophys. Res. Commun. 2001, 289 (2), 558-563. (d) Aoki S. Matsui K. Tanaka K. Satari R. Kobayashi M. Lembehyne A, a novel neuritogenic polyacetylene, from a marine sponge of Haliclona sp. Tetrahedron. 2000, 56 (51), 9945-9948.
11. Recent photoaffinity labeling experiments have identified a 30 kDa protein from Neuro–2A cells as the target of the natural product lembehyne A. Aoki, S.; Matsui, K.; Takata, T.; Kobayashi, M. In situ photoaffinity labeling of the target protein for lembehyne A, a neuronal differentiation inducer. FEBS Lett. 2003, 544 (1-3), 223-7.
12. Searle, P. A.; Molinski, T. F. Five new alkaloids from the tropical ascidian, Lissoclinum sp. Lissoclinotoxin A is chiral. J. Org. Chem. 1994, 59, 6600-6605.
13. Jones, R. N.; Barry, A. L.; Gavan, T. L.; Washington_III, J. A. In Manual of Clinical Microbiology; 4 th. ed.; Lennette, A., Balows, A., Hausler, W. J., Shadomy, H. J., Eds.; American Society of Microbiology: Washington, D.C., 1985.
14. MTS: (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt), Promega CellTiter 96® Aqueous cell proliferation assay, Technical Bulletin No. 169.
15. Compounds were assayed with compounds in DMSO (final concentration, 1% v/v) and run against etoposide as positive control. HCT-116 cells were incubated in 96-well plates for 72 h before addition of MTS. Well absorbances (λ 490 nm) were corrected for background and expressed as a percentage of the negative control (DMSO, only).