|A new polyunsaturated brominated fatty acid from a Haliclona sponge.|
|Jump to Full Text|
|PMID: 20098595 Owner: NLM Status: MEDLINE|
|A new polyunsaturated brominated fatty acid possessing acetylenic bonds 1 was isolated from the Indonesian sponge Haliclona sp. The structure of compound 1 was elucidated by analyzing its spectral data. It showed moderate cytotoxicity against cultured cells.|
|Satoe Aratake; Agus Trianto; Novriyandi Hanif; Nicole J de Voogd; Junichi Tanaka|
Related Documents :
|19115065 - Novel biotransformation process of podophyllotoxin to produce podophyllic acid and picr...
17342585 - Investigations of medicinal plants of euphorbiaceae and thymelaeaceae occurring and use...
14738395 - Three new oleanane-type triterpenes from ludwigia octovalvis with cytotoxic activity ag...
1367885 - Triterpene saponins from the roots of ampelozizyphus amazonicus.
6767535 - Vitamin k-dependent gamma-carboxyglutamic acid formation by mouse renal adenocarcinoma ...
2169205 - Amiloride and taurine inhibit cholate-induced hco3(-)-rich choleresis in perfused rat l...
|Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-11-02|
|Title: Marine drugs Volume: 7 ISSN: 1660-3397 ISO Abbreviation: Mar Drugs Publication Date: 2009|
|Created Date: 2010-01-25 Completed Date: 2010-06-24 Revised Date: 2013-05-31|
Medline Journal Info:
|Nlm Unique ID: 101213729 Medline TA: Mar Drugs Country: Switzerland|
|Languages: eng Pagination: 523-7 Citation Subset: IM|
|Department of Chemistry, Biology and Marine Science, University of the Ryukyus, Nishihara, Okinawa, Japan. email@example.com|
|APA/MLA Format Download EndNote Download BibTex|
isolation & purification*,
Anti-Infective Agents / chemistry, isolation & purification*, pharmacology
Cytotoxins / chemistry, isolation & purification*, pharmacology
Fatty Acids, Unsaturated / chemistry, isolation & purification*, pharmacology
Haliclona / chemistry*
Microbial Sensitivity Tests
|0/6-bromoicosa-3,5,8,13,15-pentaene-11,19-diynoic acid; 0/Alkynes; 0/Anti-Infective Agents; 0/Cytotoxins; 0/Fatty Acids, Unsaturated|
Journal ID (nlm-ta): Mar Drugs
Journal ID (publisher-id): MD
Publisher: Molecular Diversity Preservation International
? 2009 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland
Received Day: 22 Month: 9 Year: 2009
Revision Received Day: 27 Month: 10 Year: 2009
Accepted Day: 30 Month: 10 Year: 2009
collection publication date: Month: 12 Year: 2009
Electronic publication date: Day: 2 Month: 11 Year: 2009
Volume: 7 Issue: 4
First Page: 523 Last Page: 527
PubMed Id: 20098595
Publisher Id: marinedrugs-07-00523
|A New Polyunsaturated Brominated Fatty Acid from a Haliclona Sponge|
|Nicole J. de Voogd4|
1 Department of Chemistry, Biology and Marine Science, University of the Ryukyus, Nishihara, Okinawa 903-0213, Japan; E-Mail:
2 Department of Marine Science, Diponegoro University, Semarang 50234, Indonesia; E-Mail:
3 Department of Chemistry, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan; E-Mail:
4 Naturalis, National Museum of Natural History, PO Box 9517, 2300 RA Leiden, The Netherlands; E-Mail:
|* Author to whom correspondence should be addressed; E-Mail:
firstname.lastname@example.org; Tel.: +81-98-895-8560; Fax: +81-98-895-8565.
To date a number of linear acetylenic compounds have been isolated from marine organisms. Among them, sponges are the most prolific sources of molecules of this class. Representative members retain unique structures and show biomedical potential, e.g., lembehynes showing neuritogenic activity , petrosynol and petrosynolic acid inhibiting reverse transcriptase of human immunodeficiency virus , pellynols showing potent cytotoxicity , and a thiophene-containing fatty acid showing antimicrobial activity . In our quest to discover new bioactive molecules from marine invertebrates of the Okinawan and Indonesian coral reefs, we screened extracts prepared from specimens collected around Alor Island, Indonesia. A lipophilic extract of the sponge Haliclona sp. showed cytotoxicity against cultured cells, and hence, we isolated its active constituent, the structure of which is the subject of this manuscript.
The sponge was extracted with acetone. Its lipophilic extract was separated on a silica gel column, followed by reverse-phase HPLC to yield compound 1 as an oil, which gradually decomposes during handling. The molecular formula of the compound was C20H21BrO2 by ESITOFMS, indicating ten degrees of unsaturation. This could be accounted for by the presence of five olefins (ten signals from ? 110.1 to 140.9), two acetylenes (? 68.9 d, 80.0 s, 83.6 s, 89.6 s), and one carboxylic acid (? 174.0; 1,713 cm?1). Strong UV absorption at 256 nm suggested the presence of conjugated systems.
Four partial structures i?iv were revealed by inspecting COSY cross peaks (Table 1): (i) a diene (a vinyl proton at ? 6.67 (H-5) next to cis olefinic protons at ? 5.67 and 6.23) with a methylene at ? 3.20 (H-2), (ii) a double bond (? 5.47 and 5.63; H-8,9) flanked by two methylenes at ? 3.39 (H-7) and 3.15 (H-10), (iii) conjugated trans double bonds (? 5.52, 6.50, 6.13, and 5.79; H-13 to H-16) with a methylene at ? 2.31 (H-17), and (iv) a terminal acetylenic proton at ? 1.90 (H-20) with a methylene at ? 2.28 (H-18). The remaining substituted acetylene should be placed between units ii and iii because HMBC correlations H-10/C-11,12 and H-14/C-12 were observed. Additional HMBC correlations enabled us to connect the following units: i and ii (H-5/C-6,7 and H-7/C-5,6), iii and iv (H-17/C-18 and H-18/C-17), and i and the carboxylic acid (H-2/C-1). Bromine was placed at the sole quaternary olefinic carbon at C-6. NOE between H-7 and H-4 determined 5E configuration, while 8Z configuration was assigned by the J value (10.5 Hz) between H-8 and H-9 with decoupling experiments. Therefore, the entire structure was elucidated to be 6-bromo-icosa-3Z,5E,8Z,13E,15E-pentaene-11,19-diynoic acid. Although more than twenty fatty acids with bromination at C-6 have been reported [5?11], compound 1 had the highest unsaturation degree of this class.
We evaluated the cytotoxicity of the purified molecule 1 against NBT-T2 rat bladder epithelial cells, and the IC50 value was estimated to be 36 ?g/mL. This weaker activity than the original extract was because of the presence of other toxic components and/or decomposition of the molecule during the assay.
ESIMS was measured on a PE QSTAR mass spectrometer. FTIR and UV spectra were obtained on Varian FTS-3000 and Hitachi U-2000 instruments. 1H- and 13C- as well as 2D NMR spectra were obtained on a Jeol A500 spectrometer in CDCl3 with reference to an internal standard of TMS. Chemical shifts and coupling constants were expressed in ? and Hz.
The sponge shown below in Figure 2 was collected at a depth range of 20?35 m by hand during scuba diving on the strait between Alor and Pantar Islands, Nusa Tengara Timur, Indonesia. The specimen was identified by one of the authors (NJdV) as Haliclona sp., Chalinidae, Haplosclerida, and deposited at Naturalis, National Museum of Natural History, Leiden, the Netherlands, with a code RMNH POR 4825.
The frozen sponge (wet weight, 43.4 g) was cut and steeped in acetone (200 mL) three times. The combined acetone solution was concentrated under vacuum, and the resulting residue was partitioned between EtOAc and water. The organic layer yielded 365 mg of a crude oil showing cytotoxicity at 1 ?g/mL. The extract was separated on a silica gel with stepwise elution (Hexane-EtOAc: 1?0, 10?1, 1?1, 0?1, and MeOH) to give six fractions. Of these, the fifth fraction (18.5 mg) eluted with EtOAc was further separated by reverse-phase HPLC (RP-18, MeOH-H2O, 50-1) to yield compound 1 (7.9 mg). An additional amount was obtained from recollected specimens.
Oil. HRESIMS m/z 395.0604, 397.0601 (calcd. for C20H21BrO2Na, 395.0623, 397.0602); FTIR (neat) 3,295, 3,026, 2,925, 2,361, 2,214, 2,116, 1,713, 1,593 cm?1; UV ?max 256 nm (log? 4.5, MeOH); and 1H- and 13C-NMR see Table 1.
NBT-T2 rat bladder epithelial cells (BRC-1370, purchased from Riken BioResource Center) were cultured in DMEM supplemented with 10% heat-inactivated fetal bovine serum and antimicrobial agents using a standard protocol and seeded in 200 ?L wells. After preincubation (37 ?C, 24 h), cells were exposed to graded concentrations of compounds in duplicate (37 ?C, 48 h). The cells were treated with MTT solution (15 ?L, 5 mg/mL in PBS) after removal of the medium and incubated for 3 h. Residual formozan was dissolved in DMSO (100 ?L) and absorbance was measured using a Tecan Sunrise microplate reader at 560 nm. IC50 values were estimated by plotting absorbance values against concentrations.
Samples Availability: Distribution is not planned, because of the unstable nature of the molecule.
We thank PharmaMar S.A. for their support.
|1..||Aoki S,Matsui K,Wei H,Murakami N,Kobayashi M. Structure-activity relationship of neuritogenic spongean acetylene alcohols, lembehynesTetrahedronYear: 20025854175422|
|2..||Rashid MA,Gustafson KR,Boyd NR,Pellynol I. A new cytotoxic polyacetylene from the sponge Pellina spNat Prod LettYear: 200014387392|
|3..||Isaacs S,Kashman Y,Loya S,Hizi A,Loya Y. Petrosynol and petrosolic acid, two novel natural inhibitors of the reverse transcriptase of human immunodeficiency virus from Petrosia spTetrahedronYear: 1993491043510438|
|4..||Tianero MDB,Hanif N,de Voogd NJ,van Soest RWM,Tanaka J. A new antimicrobial fatty acid from the Calcareous sponge Paragrantia cf. waguensisChem. BiodiversYear: 200961374137719774600|
|5..||Brantley SE,Molinski TF,Preston CM,DeLong EF. Brominated acetylenic fatty acids from Xestospongia sp., a marine sponge-bacteria associationTetrahedronYear: 19955176677672|
|6..||Carballeira NM,Shalabi F. Novel brominated phospholipid fatty acids from the Caribbean sponge Petrosia spJ Nat ProdYear: 1993567397468326322|
|7..||Garson MJ,Zimmermann MP,Hoberg M,Larsen RM,Battershill CN,Murphy PT. Isolation of brominated long-chain fatty acids from the phospholipids of the tropical marine spongeAmphimedon terpenensis LipidsYear: 19932810111014|
|8..||Ichiba T,Scheuer PJ,Kelly-Borges M. Sponge-derived polyunsaturated C16 di- and tribromocarboxylic acidsHelv Chim ActaYear: 19937628142816|
|9..||Garson MJ,Zimmermann MP,Battershill CN,Holden JL,Murphy PT. The distribution of brominated long-chain fatty acids in sponge and symbiont cell types from the tropical marine spongeAmphimedon terpenensis LipidsYear: 199429509516|
|10..||Li Y,Ishibashi M,Sasaki T,Kobayashi J. New bromine-containing unsaturated fatty acid derivatives from the Okinawan marine sponge Xestospongia spJ Chem Res (S)Year: 1995126127|
|11..||Mansoor TA,Bae BH,Hong J,Lee C-O,Im KS,Jung JH. New fatty acid derivatives from Homaxinella sp., a marine spongeLipidsYear: 20054098198516329471|
Keywords: sponge, fatty acid, cytotoxicity.
Previous Document: Preliminary characterization of extracellular allelochemicals of the toxic marine dinoflagellate Ale...
Next Document: Lyngbyastatins 8-10, elastase inhibitors with cyclic depsipeptide scaffolds isolated from the marine...