Amphimic acids and related long-chain fatty acids as DNA topoisomerase I inhibitors from an Australian sponge, Amphimedon sp.: Isolation, structure, synthesis, and biological evaluation

Nemoto, Takayuki; Yoshino, G.; Ojika, Makoto; Sakagami, Youji

doi:10.1016/s0040-4020(97)10099-0

Cited by 72 publications

(45 citation statements)

References 21 publications

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“…Sakagami and coworkers have focused on the identification of topo I inhibitors from marine sources, using a primary bioassay that contains a camptothecin-resistant recombinant human topo I enzyme and the DNA substrate supercoiled plasmid pBR322 [144,146]. Bioassayguided fractionation has led to the isolation of two ceramide sulfates (topo I -IC 50 = 0.4 and 0.2 μM, respectively) from a Japanese collection of the bryozoan Watersipora cucullata [147], and a series of related amphimic acids from an Australian sponge of the genus Amphimedon (topo I -IC 50 s range from 0.47 to 6.7 μM) [146].…”

Section: Topoisomerasesmentioning

confidence: 99%

“…Bioassayguided fractionation has led to the isolation of two ceramide sulfates (topo I -IC 50 = 0.4 and 0.2 μM, respectively) from a Japanese collection of the bryozoan Watersipora cucullata [147], and a series of related amphimic acids from an Australian sponge of the genus Amphimedon (topo I -IC 50 s range from 0.47 to 6.7 μM) [146]. Representative structures of marine metabolites found to inhibit topoisomerases are shown in Fig.…”

Section: Topoisomerasesmentioning

confidence: 99%

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Mechanism Targeted Discovery of Antitumor Marine Natural Products

Nagle¹,

Zhou²,

Mora³

et al. 2004

Current Medicinal Chemistry

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Antitumor drug discovery programs aim to identify chemical entities for use in the treatment of cancer. Many strategies have been used to achieve this objective. Natural products have always played a major role in anticancer medicine and the unique metabolites produced by marine organisms have increasingly become major players in antitumor drug discovery. Rapid advances have occurred in the understanding of tumor biology and molecular medicine. New insights into mechanisms responsible for neoplastic disease are significantly changing the general philosophical approach towards cancer treatment. Recently identified molecular targets have created exciting new means for disrupting tumor-specific cell signaling, cell division, energy metabolism, gene expression, drug resistance, and blood supply. Such tumor-specific treatments could someday decrease our reliance on traditional cytotoxicity-based chemotherapy and provide new less toxic treatment options with significantly fewer side effects. Novel molecular targets and state-of-the-art molecular mechanism-based screening methods have revitalized antitumor research and these changes are becoming an ever-increasing component of modern antitumor marine natural products research. This review describes marine natural products identified using tumor-specific mechanism-based assays for regulators of angiogenesis, apoptosis, cell cycle, macromolecule synthesis, mitochondrial respiration, mitosis, multidrug efflux, and signal transduction. Special emphasis is placed on natural products directly discovered using molecular mechanism-based screening.

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Section: Topoisomerasesmentioning

confidence: 99%

Section: Topoisomerasesmentioning

confidence: 99%

Mechanism Targeted Discovery of Antitumor Marine Natural Products

Nagle¹,

Zhou²,

Mora³

et al. 2004

Current Medicinal Chemistry

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“…These very long-chain D5,9 fatty acids are of pharmacological interest, since they are very good topoisomerase I inhibitors (IC 50 0.9-1.3 lM) [11], display cytotoxicity, and more recently we have shown that they inhibit the enoyl-ACP reductase (Fab I) enzyme of Plasmodium falciparum (malarial parasite) with an IC 50 of 0.35 lM [12]. Therefore, fatty acids containing both an a-methoxy functionality and a D5,9 double bond in a single acyl chain could be of considerable interest, not only as fatty acids with a unique and novel biosynthetic origin, but also as worthwhile marine natural products for pharmacological studies.…”

Section: Introductionmentioning

confidence: 99%

Identification of Novel α‐Methoxylated Phospholipid Fatty Acids in the Caribbean Sponge Erylus goffrilleri

Carballeira

Oyola

Vicente

et al. 2007

Lipids

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The phospholipid fatty acid composition of the Caribbean sponge Erylus goffrilleri is described for the first time. A total of 70 fatty acids with chain lengths between 13 and 29 carbons were identified in the sponge. Methyl-branched fatty acids predominated in E. goffrilleri suggesting the presence of a considerable number of bacterial symbionts. The novel fatty acids (5Z,9Z)-2-methoxy-5,9-hexadecadienoic acid, (5Z,9Z)-2-methoxy-5,9-octadecadienoic acid, (5Z,9Z)-2-methoxy-5,9-nonadecadienoic acid, and (5Z,9Z)-2-methoxy-5,9-eicosadienoic acid are described for the first time in the literature. In addition, the iso-methyl-branched fatty acids (9Z)-2-methoxy-15-methyl-9-hexadecenoic acid and (5Z,9Z)-2-methoxy-15-methyl-5,9-hexadecadienoic acid, also identified in E. goffrilleri, were identified for the first time in nature. Based on the identified metabolites it is proposed that the unprecedented biosynthetic sequence: i-17:1Delta9 --> 2-OMe-i-17:1Delta9 --> 2-OMe-i-17:2Delta5,9 might be responsible for the biosynthesis of the novel iso-alpha-methoxylated fatty acids in E. goffrilleri.

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“…[1][2][3][4][5][6][7][8][9] Topoisomerase I is a key enzyme in the breaking and fixing of DNA strands and is involved in making the necessary topological changes to DNA for key cellular processes such as replication, transcription, and recombination. 1 Topoisomerases have also evolved as key cellular targets for the development of effective anticancer drugs.…”

Section: Introductionmentioning

confidence: 99%

“…1 Other interesting topo-I lipid inhibitors include conjugated C 18 and eicosapentaenoic fatty acids, 2,4 very-long chain (C 26 -C 30 ) ∆5,9 fatty acids, 5,6 and phospholipids containing unsaturated fatty acids. 7 While most of the fatty acid topoisomerase-I inhibitory work has been performed with straight-chain fatty acids, there is just one report dealing with the topoisomerase I inhibitory activity of methyl-branched iso and anteiso fatty acids.…”

Section: Introductionmentioning

confidence: 99%

An improved synthesis for the (Z)-14-methyl-9-pentadecenoic acid and its topoisomerase I inhibitory activity

Carballeira¹,

Sanabria²,

Oyola³

2006

Arkivoc

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An improved synthesis for the (Z)-14-methyl-9-pentadecenoic acid was developed based on the appropriate use of (trimethylsilyl)acetylene as the key reagent in the synthesis. The reported synthesis started with commercially available 8-bromo-1-octanol and furnished the desired acid in seven steps and in a 16% overall yield, a significant improvement over the previous reported synthesis for this fatty acid. The synthesis reported herein afforded sufficient amounts to study the acid topoisomerase I inhibitory potential and it was found that the title acid inhibits the human placenta DNA topoisomerase I enzyme at concentrations of 500 µM.

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Amphimic acids and related long-chain fatty acids as DNA topoisomerase I inhibitors from an Australian sponge, Amphimedon sp.: Isolation, structure, synthesis, and biological evaluation

Cited by 72 publications

References 21 publications

Mechanism Targeted Discovery of Antitumor Marine Natural Products

Mechanism Targeted Discovery of Antitumor Marine Natural Products

Identification of Novel α‐Methoxylated Phospholipid Fatty Acids in the Caribbean Sponge Erylus goffrilleri

An improved synthesis for the (Z)-14-methyl-9-pentadecenoic acid and its topoisomerase I inhibitory activity

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