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2017
Le, TC, Yim CY, Park S, Katila N, Yang I, Song MC, Yoon YJ, Choi DY, Choi H, Nam SJ, Fenical W.  2017.  Lodopyridones B and C from a marine sediment-derived bacterium Saccharomonospora sp. Bioorganic & Medicinal Chemistry Letters. 27:3123-3126.   10.1016/j.bmcl.2017.05.035   AbstractWebsite

HPLC-UV guided isolation of the culture broth of a marine bacterium Saccharomonospora sp. CNQ-490 has led to the isolation of two new natural products, lodopyridones B and C (1 and 2) along with the previously reported lodopyridone A (3). Their chemical structures were established from the interpretation of 2D NMR spectroscopic data and the comparison of NMR data with the lodopyridone A (3). Lodopyridones B and C (1 and 2) possess the thiazole, and chloroquinoline groups which are characteristic features of these molecules. Lodopyridones A-C show weak inhibitory activities on the beta-site amyloid precursor protein cleaving enzyme 1 (BACE1). (c) 2017 Elsevier Ltd. All rights reserved.

Kumar, A, Borgen M, Aluwihare LI, Fenical W.  2017.  Ozone-activated halogenation of mono- and dimethylbipyrrole in seawater. Environmental Science & Technology. 51:589-595.   10.1021/acs.est.6b03601   AbstractWebsite

Polyhalogenated N-methylbipyrroles of two different structure classes have been detected worldwide in over 100 environmental samples including seawater, bird eggs, fish, dolphin blubber, and in the breast milk of humans that consume seafood. These molecules are concentrated in the fatty tissues in comparable abundance to some of the most important anthropogenic contaminants, such as the halogenated flame-retardants and pesticides. Although the origin of these compounds is still unknown, we present evidence that the production of these materials can involve the direct ozone activated seawater halogenation of N-methylbipyrrole precursors. This observation shows that environmental polyhalogenated bipyrroles can be produced via an abiotic process, and implies that the ozone activated halogenation of a variety of natural and anthropogenic seawater organics may be a significant process occurring in surface ocean waters.

2015
Puyana, M, Pawlik J, Blum J, Fehical W.  2015.  Metabolite variability Caribbean sponges of the genus Aplysina. Revista Brasileira De Farmacognosia-Brazilian Journal of Pharmacognosy. 25:592-599.   10.1016/j.bjp.2015.08.002   AbstractWebsite

Sponges of the genus Aplysina are among the most common benthic animals on reefs of the Caribbean, and display a wide diversity of morphologies and colors. Tissues of these sponges lack mineralized skeletal elements, but contain a dense spongin skeleton and an elaborate series of tyrosine-derived brominated alkaloid metabolites that function as chemical defenses against predatory fishes, but do not deter some molluscs. Among the earliest marine natural products to be isolated and identified, these metabolites remain the subject of intense interest for commercial applications because of their activities in various bioassays. In this study, crude organic extracts from 253 sponges from ten morphotypes among the species Aplysina archeri, Aplysina bathyphila, Aplysina cauliformis, Aplysina fistularis, Aplysina fulva, A. insularis, and Aplysina lacunosa were analyzed by liquid chromatographymass spectrometry (LCMS) to characterize the pattern of intra- and interspecific variabilities of the twelve major secondary metabolites present therein. Patterns across Aplysina species ranged from the presence of mostly a single compound, fistularin-3, in A. cauliformis, to a mixture of metabolites present in the other species. These patterns did not support the biotransformation hypothesis for conversion of large molecular weight molecules to smaller ones for the purpose of enhanced defense. Discriminant analyses of the metabolite data revealed strong taxonomic patterns that support a close relationship between A. fistularis, A. fulva and A. insularis, while two morphotypes of A. cauliformis (lilac creeping vs. brown erect) were very distinct. Two morphotypes of A. lacunosa, one with hard tissue consistency, the other soft and thought to belong to a separate genus (Suberea), had very similar chemical profiles. Of the twelve metabolites found among samples, variation in fistularin-3, dideoxyfistularin-3 and hydroxyaerothionin provided the most predictive influence in decreasing order. Except for one morphotype, weak relationships were found from within-morphotype analyses of metabolite concentrations as a function of geographic location (Florida, N Bahamas, S Bahamas) and depth (<10m, 1020m, >20m). Our data suggest that metabolite profiles are strongly influenced by sponge phenotype rather than by the diverse microbiome which many Aplysina species share. (C) 2015 Sociedade Brasileira de Earmacognosia. Published by Elsevier Editora Ltda. All rights reserved.

2014
Trzoss, L, Fukuda T, Costa-Lotufo LV, Jimenez P, La Clair JJ, Fenical W.  2014.  Seriniquinone, a selective anticancer agent, induces cell death by autophagocytosis, targeting the cancer-protective protein dermcidin. Proceedings of the National Academy of Sciences of the United States of America. 111:14687-14692.   10.1073/pnas.1410932111   AbstractWebsite

Natural products continue to provide vital treatment options for cancer. Although their translation into chemotherapeutics is complex, collaborative programs continue to deliver productive pipelines for cancer chemotherapy. A new natural product, seriniquinone, isolated from a marine bacterium of the genus Serinicoccus, demonstrated potent activity over a select set of tumor cell lines with particular selectivity toward melanoma cell lines. Upon entering the cell, its journey began by localization into the endoplasmic reticulum. Within 3 h, cells treated with seriniquinone underwent cell death marked by activation of autophagocytosis and gradually terminated through a caspase-9 apoptotic pathway. Using an immunoaffinity approach followed by multipoint validation, we identified the target of seriniquinone as the small protein, dermcidin. Combined, these findings revealed a small molecule motif in parallel with its therapeutic target, whose potential in cancer therapy may be significant. This discovery defines a new pharmacophore that displayed selective activity toward a distinct set of cell lines, predominantly melanoma, within the NCI 60 panel. This selectivity, along with the ease in medicinal chemical modification, provides a key opportunity to design and evaluate new treatments for those cancers that rely on dermcidin activity. Further, the use of dermcidin as a patient preselection biomarker may accelerate the development of more effective personalized treatments.

1999
Vervoort, HC, Fenical W, Keifer PA.  1999.  A cyclized didemnimide alkaloid from the Caribbean ascidian Didemnum conchyliatum. Journal of Natural Products. 62:389-391.   10.1021/np980409q   AbstractWebsite

A novel, cyclized alkaloid of the didemnimide class, 5, has been isolated from extracts of the Caribbean ascidian Didemnum conchyliatum. The structure of 5 was assigned using combined spectral methods that emphasized one- and two-dimensional NMR methods. The new alkaloid is the cyclization product of didemnimide A (1) formed via a C-2 indole condensation with the imidazole nitrogen.

Moore, BS, Trischman JA, Seng D, Kho D, Jensen PR, Fenical W.  1999.  Salinamides, antiinflammatory depsipeptides from a marine streptomycete. Journal of Organic Chemistry. 64:1145-1150.   10.1021/jo9814391   AbstractWebsite

In addition to the previously reported antiinflammatory agents salinamides A and B from the marine isolate Streptomyces sp. CNB-091, three minor peptides are described. Their total structures were established using a combination of spectral and chemical techniques. Revised structures are presented for the bicyclic depsipeptides salinamides A and B on the basis of the analysis of the dansylated salinamide A hydrolysate by chiral capillary electrophoresis. The fermentation yield of salinamide D, which contains a D-valine residue in place of the D-isoleucine moiety in salinamide A, can be dramatically increased 30-fold by supplementing the growth media with L-valine. Salinamides C and E are monocyclic depsipeptides that are likely methylated byproducts of salinamide A biosynthetic intermediates.

1998
Toske, SG, Jensen PR, Kauffman CA, Fenical W.  1998.  Aspergillamides A and B: Modified cytotoxic tripeptides produced by a marine fungus of the genus Aspergillus. Tetrahedron. 54:13459-13466.   10.1016/s0040-4020(98)00829-1   AbstractWebsite

Two isomeric linear peptides, aspergillamides A and B (1, 2), were isolated from the mycelium of a cultured marine fungus of the genus Aspergillus. The producing strain (designated CNC-120), was obtained from a saline lake sediment sample collected from Acklins Island. the Bahamas. The structures of the new peptides were elucidated using comprehensive 2D NMR methods. At 25 degrees C, in both acetone and dimethylsulfoxide, aspergillamide A exists as a 1:1 mixture of trans- and cis-amide rotational isomers (1a and 1b). Under identical conditions, aspergillamide B is predominantly in the cis-amide form. The absolute stereochemistries of the amino acids in aspergillamide A were assigned as L by hydrolysis and comparison with commercial standards. Aspergillamide A showed modest irt virro cytotoxicity [IC50 = 16 mu g/ml] toward the human colon carcinoma cell line HCT-116. (C) 1998 Elsevier Science Ltd. All rights reserved.

1997
Chanas, B, Pawlik JR, Lindel T, Fenical W.  1997.  Chemical defense of the Caribbean sponge Agelas clathrodes (Schmidt). Journal of Experimental Marine Biology and Ecology. 208:185-196.   10.1016/s0022-0981(96)02653-6   AbstractWebsite

Marine sponges have been a rich source of natural products, but only in recent years have studies been undertaken to evaluate the ecological functions of these compounds. Previously, we found that crude organic extracts of the tissues of 6 species of the genus Agelas from the Caribbean were all strongly unpalatable to a predatory reef fish in aquarium assays. In this study, we used bioassay-directed isolation techniques to identify the deterrent metabolites in one of these species, Agelas clathrodes (Schmidt). Crude organic extracts of A. clathrodes at natural concentrations deterred feeding of the reef fish Thalassoma bifasciatum (Bloch) in aquarium assays, and of a natural suite of reef fishes in field assays. Separation of the crude extract by column chromatography yielded a series of fractions, of which only the polar fractions were deterrent in both aquarium and field assays. Two previously described compounds, oroidin (1) and 4,5-dibromopyrrol-2-carboxylic acid (2), were identified by high resolution mass spectrometry and NMR spectrometry as the deterrent metabolites in the active fractions. Purified samples of both compounds deterred feeding in aquarium assays, both separately and in combination, at concentrations found in the sponge tissue. In addition, both compounds were identified by analytical thin-layer chromatography as constituents of the crude extracts of A. conifera (Schmidt), A. dispar Duchassaing and Michelotti, A. inaequalis Pulitzer-Finali, A. sceptrum (Lamarck), and A. wiedenmeyeri Alcolado. These results suggest that sponges of the genus Agelas share a common chemical defense against fish predators.

1994
Frankmolle, WP, Fenical W.  1994.  Isolation of the chlorophyll-related pigment isochlorin-e4 from the tropical red alga Dasya pedicellata. Phytochemistry. 36:361-364. AbstractWebsite

Isochlorin-e(4), a blue-green pigment related to the chlorophylls, has been isolated as a major metabolite from the tropical marine red alga Dasya pedicellata. The structure of isochlorin-e(4) was assigned on the basis of comprehensive 2D C-13 and H-1 NMR analyses. Although isochlorin-e(4) has been prepared by synthesis, this appears to be the first report of its occurrence in nature.

1993
Mayer, AMS, Paul VJ, Fenical W, Norris JN, Decarvalho MS, Jacobs RS.  1993.  Phospholipase A2 inhibitors from marine algae. Hydrobiologia. 261:521-529. AbstractWebsite

Twelve out of twenty-nine compounds isolated from benthic marine algae from the phyla Chlorophyta, Phaeophyta and Rhodophyta have been found to be potent inhibitors of bee venom derived phospholipase A2 (PLA2) (> 50 %) in the muM range. The compounds investigated were from: Bryopsis pennata, Rhipocephalus phoenix, Caulerpa prolifera, C. racemosa, C. bikinensis, Cymopolia barbata, Laurencia ef. palisada, Laurencia sp., Ochtodes crockeri, Liagora farinosa, Sphaerococcus coronipifolius, Phacelocarpus labillardieri, Dictyota sp., Bifurcaria galapagensis, Stypopodium zonale, Dictyopteris undulata, Stoechospermum marginatum, Dictyopteris divaricata, Dilophusfasciola and Dilophus sp. This is the first report of bee venom PLA2 inhibition in vitro by pure compounds isolated from marine algae.