Aldisine Alkaloids from the Philippine Sponge Stylissa massa Are Potent Inhibitors of Mitogen-Activated Protein Kinase Kinase-1 (MEK-1)

Taşdemir, Deniz; Mallon, Robert; Greenstein, Michael; Feldberg, Larry; Kim, Steven C.; Collins, Karen; Wojciechowicz, Donald; Mangalindan, Gina C.; Concepción, Gisela P.; Harper, Mary Kay; Ireland, Chris M.

doi:10.1021/jm0102856

Cited by 128 publications

(76 citation statements)

References 19 publications

(45 reference statements)

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“…Stylissa massa belongs to the family Dictyonellidae, which is one of the better investigated groups of marine invertebrates from the perspective of natural products chemistry, and some of the identified compounds have known ecological roles (Becerro et al, 2003). The most prominent natural products isolated from S. massa include the alkaloids oroidin, debromohymenialdisine, hymenialdisine (Tasdemir et al, 2002), sceptrin (Mohammed et al, 2006), hymenidin (Kobayashi et al, 1986), and palau'amine (Kinnel et al, 1993). The aim of this study was to assess the variation in secondary metabolite production in S. massa at various spatial scales, including local, regional, and biogeographic.…”

Section: Introductionmentioning

confidence: 99%

Spatial Variability in Secondary Metabolites of the Indo-Pacific Sponge Stylissa massa

Rohde¹,

Gochfeld

Ankisetty

et al. 2012

J Chem Ecol

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Chemical diversity represents a measure of selective pressures acting on genotypic variability. In order to understand patterns of chemical ecology and biodiversity in the environment, it is necessary to enhance our knowledge of chemical diversity within and among species. Many sponges produce variable levels of secondary metabolites in response to diverse biotic and abiotic environmental factors. This study evaluated intra-specific variability in secondary metabolites in the common Indo-Pacific sponge Stylissa massa over various geographic scales, from local to ocean basin. Several major metabolites were quantified in extracts from sponges collected in American Samoa, Pohnpei, Saipan, and at several sites and depths in Guam. Concentrations of several of these metabolites varied geographically across the Pacific basin, with American Samoa and Pohnpei exhibiting the greatest differences, and Guam and Saipan more similar to each other. There were also significant differences in concentrations among different sites and depths within Guam. The crude extract of S. massa exhibited feeding deterrence against the omnivorous pufferfish Canthigaster solandri at natural concentrations, however, none of the isolated compounds was deterrent at the maximum natural concentrations observed, nor were mixtures of these compounds, thus emphasizing the need for bioassay-guided isolation to characterize specific chemical defenses. Antibacterial activity against a panel of ecologically relevant pathogens was minimal. Depth transplants, predator exclusion, and UV protection experiments were performed, but although temporal variability in compound concentrations was observed, there was no evidence that secondary metabolite concentration in S. massa was induced by any of these factors. Although the reasons behind the variability observed in the chemical constituents of S. massa are still in question, all sponges are not created equal from a chemical standpoint, and these studies provide further insights into patterns of chemical diversity within S. massa.

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Section: Introductionmentioning

confidence: 99%

Spatial Variability in Secondary Metabolites of the Indo-Pacific Sponge Stylissa massa

Rohde¹,

Gochfeld

Ankisetty

et al. 2012

J Chem Ecol

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“…They are anti-tumour (Tasdemir et al, 2002;Gordaliza, 2010) have potent antileukemic activity (Muller et al, 1985), inhibitory activity against hepatocellular carcinoma, colorectal carcinoma and breast adenocarcinoma cells (Elhady et al, 2016). They are used for the treatment of psoriasis (Pietschmann et al, 2004), as anti foulant (Pereira et al, 2002;Riberio et al, 2012), in cosmetics (Swatschek et al, 2002), for marine environmental bioremediation in integrated aquaculture practices (Milanese et al, 2003), bioremediation in polluted sea water (Stabili et al, 2006), to clear large volume of water of organic and bacterial loads in polluted sites (Ledda et al, 2014) as their pumping activity might play an important role in water purification.…”

Section: Applications Of Marine Spongesmentioning

confidence: 99%

“…Several compounds like Hymenialdisine, an alkaloid with potential against human neurodegenerative diseases have been found from S. massa. Eight alkaloids were derived from these sponges which has potential as anti-tumour (Tasdemir et al, 2002). Their extensive availability in India could be utilized for development of culture technologies.…”

Section: Some Of the Candidate Sponges For Mariculture In Indiamentioning

confidence: 99%

Cultivation of Marine Sponges with Pharmaceutical Value: Status and Future Prospects in India

Kiruba-Sankar¹,

Vinod²,

Roy³

et al. 2017

Int.J.Curr.Microbiol.App.Sci

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“…A primary assay measured the degree of MAPK phosphorylation (threonine 202 and tyrosine 204) as the end point, while a secondary assay examined Raf and MEK1 selectivity. Several thousand marine sponge extracts were screened in the primary assay for inhibitors of the Raf/MEK1/MAPK cascade, and bioassay-guided isolation led to the identification of eight pyrrole alkaloids from Philippine collections of the sponge Stylissa massa [300]. Among the five compounds, Fig.…”

Section: Egfr/ras/raf/mek/mapk Signalingmentioning

confidence: 99%

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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Aldisine Alkaloids from the Philippine Sponge Stylissa massa Are Potent Inhibitors of Mitogen-Activated Protein Kinase Kinase-1 (MEK-1)

Cited by 128 publications

References 19 publications

Spatial Variability in Secondary Metabolites of the Indo-Pacific Sponge Stylissa massa

Spatial Variability in Secondary Metabolites of the Indo-Pacific Sponge Stylissa massa

Cultivation of Marine Sponges with Pharmaceutical Value: Status and Future Prospects in India

Mechanism Targeted Discovery of Antitumor Marine Natural Products

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