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Valerie J Paul - One of the best experts on this subject based on the ideXlab platform.
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Discovery, Total Synthesis and Key Structural Elements for the Immunosuppressive Activity of Cocosolide, a Symmetrical Glycosylated Macrolide Dimer from Marine Cyanobacteria.
Chemistry: A European Journal, 2016Co-Authors: Sarath P. Gunasekera, Yang Li, Ranjala Ratnayake, Jeannette Lo, Joseph H. Reibenspies, Zhengshuang Xu, Michael J. Clare-salzler, Tao Ye, Valerie J PaulAbstract:A new dimeric macrolide xylopyranoside, cocosolide (1), was isolated from the marine cyanobacterium preliminarily identified as Symploca sp. from Guam. The structure was determined by a combination of NMR spectroscopy, HRMS, X-ray diffraction studies and Mosher's analysis of the base hydrolysis product. Its carbon skeleton closely resembles that of clavosolides A-D isolated from the sponge Myriastra clavosa, for which no bioactivity is known. We performed the first total synthesis of cocosolide (1) along with its [I±,I±]-anomer (26) and macrocyclic core (28), thus leading to the confirmation of the structure of natural 1. The convergent synthesis featured Wadsworth-Emmons cyclopropanation, Sakurai annulation, Yamaguchi macrocyclization/dimerization reaction, I±-selective glycosidation and I²-selective glycosidation. Compounds 1 and 26 potently inhibited IL-2 production in both T-cell receptor dependent and independent manners. Full activity requires the presence of the sugar moiety as well as the intact dimeric structure. Cocosolide also suppressed the proliferation of anti-CD3-stimulated T-cells in a dose-dependent manner.
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Caldora penicillata gen. nov., comb. nov. (Cyanobacteria), a pantropical marine species with biomedical relevance
Journal of Phycology, 2015Co-Authors: Niclas Engene, Ana Tronholm, Lilibeth A. Salvador-reyes, Hendrik Luesch, Valerie J PaulAbstract:: Many tropical marine cyanobacteria are prolific producers of bioactive secondary metabolites with ecological relevance and promising pharmaceutical applications. One species of chemically rich, tropical marine cyanobacteria that was previously identified as Symploca hydnoides or Symploca sp. corresponds to the traditional taxonomic definition of Phormidium penicillatum. In this study, we clarified the taxonomy of this biomedically and ecologically important cyanobacterium by comparing recently collected specimens with the original type material and the taxonomic description of P. penicillatum. Molecular phylogenetic analyses of the 16S rRNA gene and the 16S-23S internal transcribed spacer regions showed that P. penicillatum formed an independent clade sister to the genus Symploca, and distantly related to Phormidium and Lyngbya. We propose the new genus Caldora for this clade, with Caldora penicillata comb. nov. as the type species and designate as the epitype the recently collected strain FK13-1. Furthermore, the production of bioactive secondary metabolites among various geographically dispersed collections of C. penicillata showed that this species consistently produced the metabolite dolastatin 10 and/or the related compound symplostatin 1, which appear to be robust autapomorphic characters and chemotaxonomic markers for this taxon.
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veraguamides a g cyclic hexadepsipeptides from a dolastatin 16 producing cyanobacterium Symploca cf hydnoides from guam
Journal of Natural Products, 2011Co-Authors: Lilibeth A Salvador, Valerie J Paul, Jason S Biggs, Hendrik LueschAbstract:Cytotoxicity-directed purification of a Symploca cf. hydnoides sample from Cetti Bay, Guam, afforded seven new cyclic depsipeptides, veraguamides A−G (1−7), together with the known compound dolastatin 16. The planar structures of 1−7 were elucidated using NMR and MS experiments, while enantioselective HPLC and Mosher’s analysis of acid and base hydrolysates, respectively, were utilized to assign the absolute configurations of the stereocenters. Veraguamides A−G (1−7) are characterized by the presence of an invariant proline residue, multiple N-methylated amino acids, an α-hydroxy acid, and a C8-polyketide-derived β-hydroxy acid moiety with a characteristic terminus as either an alkynyl bromide, alkyne, or vinyl group. These compounds and a semisynthetic analogue (8) showed moderate to weak cytotoxic activity against HT29 colorectal adenocarcinoma and HeLa cervical carcinoma cell lines. Preliminary structure−activity relationship analysis identified several sensitive positions in the veraguamide scaffold t...
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Veraguamides A−G, Cyclic Hexadepsipeptides from a Dolastatin 16-Producing Cyanobacterium Symploca cf. hydnoides from Guam
Journal of Natural Products, 2011Co-Authors: Lilibeth A Salvador, Valerie J Paul, Jason S Biggs, Hendrik LueschAbstract:Cytotoxicity-directed purification of a Symploca cf. hydnoides sample from Cetti Bay, Guam, afforded seven new cyclic depsipeptides, veraguamides A−G (1−7), together with the known compound dolastatin 16. The planar structures of 1−7 were elucidated using NMR and MS experiments, while enantioselective HPLC and Mosher’s analysis of acid and base hydrolysates, respectively, were utilized to assign the absolute configurations of the stereocenters. Veraguamides A−G (1−7) are characterized by the presence of an invariant proline residue, multiple N-methylated amino acids, an α-hydroxy acid, and a C8-polyketide-derived β-hydroxy acid moiety with a characteristic terminus as either an alkynyl bromide, alkyne, or vinyl group. These compounds and a semisynthetic analogue (8) showed moderate to weak cytotoxic activity against HT29 colorectal adenocarcinoma and HeLa cervical carcinoma cell lines. Preliminary structure−activity relationship analysis identified several sensitive positions in the veraguamide scaffold t...
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Combinatorial strategies by marine cyanobacteria: symplostatin 4, an antimitotic natural dolastatin 10/15 hybrid that synergizes with the coproduced HDAC inhibitor largazole.
ChemBioChem, 2009Co-Authors: Kanchan Taori, Valerie J Paul, Hendrik LueschAbstract:: Combinatorial biosynthesis meets combinatorial pharmacology, cyanobacterial style: A new antimitotic natural product with features of both dolastatins 10 and 15 was isolated from the same Floridian Symploca sp. sample that produced the histone deacetylase inhibitor largazole. Both agents in combination are more effective in inhibiting cancer cell proliferation than either agent alone.
Wesley Y Yoshida - One of the best experts on this subject based on the ideXlab platform.
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isolation and structure determination of malevamide e a dolastatin 14 analogue from the marine cyanobacterium Symploca laete viridis
Journal of Natural Products, 2008Co-Authors: Beatrice Adams, Wesley Y Yoshida, Hans E Westenburg, Peter Porzgen, Emily Pittman, David F HorgenAbstract:A new depsipeptide, malevamide E (1), was isolated from field-collected colonies of the filamentous cyanobacterium Symploca laete-viridis. The gross structure of 1 was determined by spectroscopic analyses, including one- and two-dimensional NMR and accurately measured MS/MS. Chiral HPLC analyses of an acid hydrolysate of 1 allowed the stereochemical assignments of its amino acid residues, which include N-methyl-l-alanine, α-N,γ-N-dimethyl-l-asparagine, N-methyl-l-phenylalanine, l-proline, d-valine, and N-methyl-l-valine. LC-MS/MS analysis of S. laete-viridis fractions established the co-occurrence of malevamide E (1) and its homologue dolastatin 14 (2), which was previously reported in low yield from the sea hare Dolabella auricularia. Malevamide E (1) demonstrated a dose-dependent (2–45 µM) inhibition of store-operated Ca2+ entry in thapsigargin-treated human embryonic kidney (HEK) cells, indicating an inhibitory effect on Ca2+ release-activated Ca2+ (CRAC) channels.
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micromide and guamamide cytotoxic alkaloids from a species of the marine cyanobacterium Symploca
Journal of Natural Products, 2004Co-Authors: Philip G Williams, Wesley Y Yoshida, Richard E Moore, Valerie J PaulAbstract:Two new cytotoxins have been isolated from a species of marine cyanobacterium belonging to the genus Symploca that was collected in Guam. These new compounds, micromide (1) and guamamide (2), were accompanied by the known lipopeptides apramides A (3), B (4), and G (5). The planar structures of both alkaloids were elucidated by standard 2D NMR techniques, and the configurations of the amino acid-derived units in 1 were determined by chiral HPLC. The stereochemistry of the β-methoxyhexanoic acid in 1 was determined by derivatization with methyl d-mandelate, after acid hydrolysis, and comparison with synthetic standards.
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Novel Iodinated Diterpenes from a Marine Cyanobacterium and Red Alga Assemblage
Organic Letters, 2003Co-Authors: Philip G Williams, Wesley Y Yoshida, Richard E Moore, Valerie J PaulAbstract:Tasihalides A and B have been isolated from an assemblage of a marine cyanobacterium, belonging to the genus Symploca, and an unidentified red alga. The gross structures and relative stereochemistries of these diterpenes were elucidated by spectroscopic means. In addition to possessing a novel cage structure, the tasihalides represent the only examples of iodinated diterpenes in nature.
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the isolation and structure elucidation of tasiamide b a 4 amino 3 hydroxy 5 phenylpentanoic acid containing peptide from the marine cyanobacterium Symploca sp
Journal of Natural Products, 2003Co-Authors: Philip G Williams, Wesley Y Yoshida, Richard E Moore, Valerie J PaulAbstract:A new cytotoxic peptide, which displayed an IC50 value of 0.8 μM against KB cells, has been isolated from the marine cyanobacterium Symploca sp. The planar structure of tasiamide B (1), deduced by 2D NMR experiments, contains the unusual amino acid-derived residue 4-amino-3-hydroxy-5-phenylpentanoic acid (Ahppa). The configuration of 1 was deduced by HPLC analysis of degradation products.
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tasipeptins a and b new cytotoxic depsipeptides from the marine cyanobacterium Symploca sp
Journal of Natural Products, 2003Co-Authors: Philip G Williams, Wesley Y Yoshida, Richard E Moore, Valerie J PaulAbstract:Two new depsipeptides have been isolated from a Symploca sp. collected in Palau. The gross structures of tasipeptins A (1) and B (2) were determined by standard spectroscopic techniques, and the absolute configuration of the amino acid units was determined by chiral HPLC. The relative stereochemistry of the 3-amino-6-hydroxy-2-piperidone (Ahp) moiety in both structures was determined by analysis of 2,3JH,H values. Oxidation with PCC and acid hydrolysis unmasked this latent glutamic acid moiety, allowing for elucidation of the total configuration of 1 and 2. Tasipeptins A (1) and B (2) were cytotoxic toward KB cells with IC50 values of 0.93 and 0.82 μM, respectively.
Hendrik Luesch - One of the best experts on this subject based on the ideXlab platform.
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Caldora penicillata gen. nov., comb. nov. (Cyanobacteria), a pantropical marine species with biomedical relevance
Journal of Phycology, 2015Co-Authors: Niclas Engene, Ana Tronholm, Lilibeth A. Salvador-reyes, Hendrik Luesch, Valerie J PaulAbstract:: Many tropical marine cyanobacteria are prolific producers of bioactive secondary metabolites with ecological relevance and promising pharmaceutical applications. One species of chemically rich, tropical marine cyanobacteria that was previously identified as Symploca hydnoides or Symploca sp. corresponds to the traditional taxonomic definition of Phormidium penicillatum. In this study, we clarified the taxonomy of this biomedically and ecologically important cyanobacterium by comparing recently collected specimens with the original type material and the taxonomic description of P. penicillatum. Molecular phylogenetic analyses of the 16S rRNA gene and the 16S-23S internal transcribed spacer regions showed that P. penicillatum formed an independent clade sister to the genus Symploca, and distantly related to Phormidium and Lyngbya. We propose the new genus Caldora for this clade, with Caldora penicillata comb. nov. as the type species and designate as the epitype the recently collected strain FK13-1. Furthermore, the production of bioactive secondary metabolites among various geographically dispersed collections of C. penicillata showed that this species consistently produced the metabolite dolastatin 10 and/or the related compound symplostatin 1, which appear to be robust autapomorphic characters and chemotaxonomic markers for this taxon.
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Largazole: From discovery to broad-spectrum therapy
Natural Product Reports, 2012Co-Authors: Jiyong Hong, Hendrik LueschAbstract:Covering up to 2011 The cyclic depsipeptide largazole from a cyanobacterium of the genus Symploca is a marine natural product with a novel chemical scaffold and potently inhibits class I histone deacetylases (HDACs). Largazole possesses highly differential growth-inhibitory activity, preferentially targeting transformed over non-transformed cells. The intriguing structure and biological activity of largazole have attracted strong interest from the synthetic chemistry community to establish synthetic routes to largazole and to investigate its potential as a cancer therapeutic. This Highlight surveys recent advances in this area with a focus on the discovery, synthesis, target identification, structure–activity relationships, HDAC8–largazole thiol crystal structure, and biological studies, including in vivo anticancer and osteogenic activities.
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veraguamides a g cyclic hexadepsipeptides from a dolastatin 16 producing cyanobacterium Symploca cf hydnoides from guam
Journal of Natural Products, 2011Co-Authors: Lilibeth A Salvador, Valerie J Paul, Jason S Biggs, Hendrik LueschAbstract:Cytotoxicity-directed purification of a Symploca cf. hydnoides sample from Cetti Bay, Guam, afforded seven new cyclic depsipeptides, veraguamides A−G (1−7), together with the known compound dolastatin 16. The planar structures of 1−7 were elucidated using NMR and MS experiments, while enantioselective HPLC and Mosher’s analysis of acid and base hydrolysates, respectively, were utilized to assign the absolute configurations of the stereocenters. Veraguamides A−G (1−7) are characterized by the presence of an invariant proline residue, multiple N-methylated amino acids, an α-hydroxy acid, and a C8-polyketide-derived β-hydroxy acid moiety with a characteristic terminus as either an alkynyl bromide, alkyne, or vinyl group. These compounds and a semisynthetic analogue (8) showed moderate to weak cytotoxic activity against HT29 colorectal adenocarcinoma and HeLa cervical carcinoma cell lines. Preliminary structure−activity relationship analysis identified several sensitive positions in the veraguamide scaffold t...
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Veraguamides A−G, Cyclic Hexadepsipeptides from a Dolastatin 16-Producing Cyanobacterium Symploca cf. hydnoides from Guam
Journal of Natural Products, 2011Co-Authors: Lilibeth A Salvador, Valerie J Paul, Jason S Biggs, Hendrik LueschAbstract:Cytotoxicity-directed purification of a Symploca cf. hydnoides sample from Cetti Bay, Guam, afforded seven new cyclic depsipeptides, veraguamides A−G (1−7), together with the known compound dolastatin 16. The planar structures of 1−7 were elucidated using NMR and MS experiments, while enantioselective HPLC and Mosher’s analysis of acid and base hydrolysates, respectively, were utilized to assign the absolute configurations of the stereocenters. Veraguamides A−G (1−7) are characterized by the presence of an invariant proline residue, multiple N-methylated amino acids, an α-hydroxy acid, and a C8-polyketide-derived β-hydroxy acid moiety with a characteristic terminus as either an alkynyl bromide, alkyne, or vinyl group. These compounds and a semisynthetic analogue (8) showed moderate to weak cytotoxic activity against HT29 colorectal adenocarcinoma and HeLa cervical carcinoma cell lines. Preliminary structure−activity relationship analysis identified several sensitive positions in the veraguamide scaffold t...
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Combinatorial strategies by marine cyanobacteria: symplostatin 4, an antimitotic natural dolastatin 10/15 hybrid that synergizes with the coproduced HDAC inhibitor largazole.
ChemBioChem, 2009Co-Authors: Kanchan Taori, Valerie J Paul, Hendrik LueschAbstract:: Combinatorial biosynthesis meets combinatorial pharmacology, cyanobacterial style: A new antimitotic natural product with features of both dolastatins 10 and 15 was isolated from the same Floridian Symploca sp. sample that produced the histone deacetylase inhibitor largazole. Both agents in combination are more effective in inhibiting cancer cell proliferation than either agent alone.
Richard E Moore - One of the best experts on this subject based on the ideXlab platform.
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micromide and guamamide cytotoxic alkaloids from a species of the marine cyanobacterium Symploca
Journal of Natural Products, 2004Co-Authors: Philip G Williams, Wesley Y Yoshida, Richard E Moore, Valerie J PaulAbstract:Two new cytotoxins have been isolated from a species of marine cyanobacterium belonging to the genus Symploca that was collected in Guam. These new compounds, micromide (1) and guamamide (2), were accompanied by the known lipopeptides apramides A (3), B (4), and G (5). The planar structures of both alkaloids were elucidated by standard 2D NMR techniques, and the configurations of the amino acid-derived units in 1 were determined by chiral HPLC. The stereochemistry of the β-methoxyhexanoic acid in 1 was determined by derivatization with methyl d-mandelate, after acid hydrolysis, and comparison with synthetic standards.
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Novel Iodinated Diterpenes from a Marine Cyanobacterium and Red Alga Assemblage
Organic Letters, 2003Co-Authors: Philip G Williams, Wesley Y Yoshida, Richard E Moore, Valerie J PaulAbstract:Tasihalides A and B have been isolated from an assemblage of a marine cyanobacterium, belonging to the genus Symploca, and an unidentified red alga. The gross structures and relative stereochemistries of these diterpenes were elucidated by spectroscopic means. In addition to possessing a novel cage structure, the tasihalides represent the only examples of iodinated diterpenes in nature.
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the isolation and structure elucidation of tasiamide b a 4 amino 3 hydroxy 5 phenylpentanoic acid containing peptide from the marine cyanobacterium Symploca sp
Journal of Natural Products, 2003Co-Authors: Philip G Williams, Wesley Y Yoshida, Richard E Moore, Valerie J PaulAbstract:A new cytotoxic peptide, which displayed an IC50 value of 0.8 μM against KB cells, has been isolated from the marine cyanobacterium Symploca sp. The planar structure of tasiamide B (1), deduced by 2D NMR experiments, contains the unusual amino acid-derived residue 4-amino-3-hydroxy-5-phenylpentanoic acid (Ahppa). The configuration of 1 was deduced by HPLC analysis of degradation products.
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tasipeptins a and b new cytotoxic depsipeptides from the marine cyanobacterium Symploca sp
Journal of Natural Products, 2003Co-Authors: Philip G Williams, Wesley Y Yoshida, Richard E Moore, Valerie J PaulAbstract:Two new depsipeptides have been isolated from a Symploca sp. collected in Palau. The gross structures of tasipeptins A (1) and B (2) were determined by standard spectroscopic techniques, and the absolute configuration of the amino acid units was determined by chiral HPLC. The relative stereochemistry of the 3-amino-6-hydroxy-2-piperidone (Ahp) moiety in both structures was determined by analysis of 2,3JH,H values. Oxidation with PCC and acid hydrolysis unmasked this latent glutamic acid moiety, allowing for elucidation of the total configuration of 1 and 2. Tasipeptins A (1) and B (2) were cytotoxic toward KB cells with IC50 values of 0.93 and 0.82 μM, respectively.
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The molecular pharmacology of symplostatin 1: A new antimitotic dolastatin 10 analog
International Journal of Cancer, 2003Co-Authors: Susan L Mooberry, Hendrik Luesch, Richard E Moore, Rachel M. Leal, Tina L. Tinley, Thomas H CorbettAbstract:Symplostatin 1, an analog of dolastatin 10, was recently isolated from cyanobacteria of the genus Symploca. Symplostatin 1 is a potent inhibitor of cell proliferation with IC50 values in the low nanomolar range and it exhibits efficacy against a variety of cancer cell types. Symplostatin 1 caused the formation of abnormal mitotic spindles and accumulation of cells in metaphase at concentrations that had only minor effects on interphase microtubules. At higher concentrations, symplostatin 1 caused the loss of interphase microtubules. Cell cycle analysis revealed that symplostatin 1 caused G2/M arrest, consistent with its effects on mitotic spindles. Symplostatin 1 initiated the phosphorylation of Bcl-2, formation of micronuclei and activation of caspase 3, indicating induction of apoptosis. The cellular effects of symplostatin 1 are consistent with other antimitotic tubulin-targeting drugs. Tubulin polymerization experiments indicated that symplostatin 1 potently inhibits the assembly of purified tubulin, suggesting that tubulin may be its intracellular target. Some microtubule-targeting agents are reported to have antiangiogenic activity and therefore the effects of symplostatin 1 on endothelial cell proliferation and invasion were evaluated. Symplostatin 1 was found to be a potent inhibitor of both endothelial cell proliferation and invasion. Because of its potent and broad activity in vitro, symplostatin 1 was evaluated in vivo. Symplostatin 1 was active against murine colon 38 and murine mammary 16/C; however, it was poorly tolerated and the mice were slow to recover from the toxicity. The data indicate that symplostatin 1 has a mechanism of action similar to dolastatin 10. © 2003 Wiley-Liss, Inc.
William H Gerwick - One of the best experts on this subject based on the ideXlab platform.
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lipopeptides from the tropical marine cyanobacterium Symploca sp
Journal of Natural Products, 2014Co-Authors: Emily Mevers, Pieter C Dorrestein, F Jake P Haeckl, Paul D Boudreau, Tara Byrum, Frederick A Valeriote, William H GerwickAbstract:A collection of the tropical marine cyanobacterium Symploca sp., collected near Kimbe Bay, Papua New Guinea, previously yielded several new metabolites including kimbeamides A–C, kimbelactone A, and tasihalide C. Investigations into a more polar cytotoxic fraction yielded three new lipopeptides, tasiamides C–E (1–3). The planar structures were deduced by 2D NMR spectroscopy and tandem mass spectrometry, and their absolute configurations were determined by a combination of Marfey’s and chiral-phase GC-MS analysis. These new metabolites are similar to several previously isolated compounds, including tasiamide (4), grassystatins (5, 6), and symplocin A, all of which were isolated from similar filamentous marine cyanobacteria.
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santacruzamate a a potent and selective histone deacetylase inhibitor from the panamanian marine cyanobacterium cf Symploca sp
Journal of Natural Products, 2013Co-Authors: Christopher Pavlik, Niclas Engene, Christina Y B Wong, Sophia Ononye, Dioxelis Lopez, Kerry L Mcphail, William H Gerwick, Marcy J BalunasAbstract:A dark brown tuft-forming cyanobacterium, morphologically resembling the genus Symploca, was collected during an expedition to the Coiba National Park, a UNESCO World Heritage Site on the Pacific coast of Panama. Phylogenetic analysis of its 16S rRNA gene sequence indicated that it is 4.5% divergent from the type strain for Symploca and thus is likely a new genus. Fractionation of the crude extract led to the isolation of a new cytotoxin, designated santacruzamate A (1), which has several structural features in common with suberoylanilide hydroxamic acid [(2), SAHA, trade name Vorinostat], a clinically approved histone deacetylase (HDAC) inhibitor used to treat refractory cutaneous T-cell lymphoma. Recognition of the structural similarly of 1 and SAHA led to the characterization of santacruzamate A as a picomolar level selective inhibitor of HDAC2, a Class I HDAC, with relatively little inhibition of HDAC4 or HDAC6, both Class II HDACs. As a result, chemical syntheses of santacruzamate A as well as a stru...
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The Carmaphycins: New Proteasome Inhibitors Exhibiting an α,β-Epoxyketone Warhead from a Marine Cyanobacterium
ChemBioChem, 2012Co-Authors: Alban R. Pereira, Hosana Maria Debonsi, Tara Byrum, Frederick A Valeriote, Andrew J. Kale, Andrew T. Fenley, Michael K. Gilson, Bradley S. Moore, William H GerwickAbstract:: Two new peptidic proteasome inhibitors were isolated as trace components from a Curacao collection of the marine cyanobacterium Symploca sp. Carmaphycin A (1) and carmaphycin B (2) feature a leucine-derived α,β-epoxyketone warhead directly connected to either methionine sulfoxide or methionine sulfone. Their structures were elucidated on the basis of extensive NMR and MS analyses and confirmed by total synthesis, which in turn provided more material for further biological evaluations. Pure carmaphycins A and B were found to inhibit the β5 subunit (chymotrypsin-like activity) of the S. cerevisiae 20S proteasome in the low nanomolar range. Additionally, they exhibited strong cytotoxicity to lung and colon cancer cell lines, as well as exquisite antiproliferative effects in the NCI60 cell-line panel. These assay results as well as initial structural biology studies suggest a distinctive binding mode for these new inhibitors.
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Symplocamide a a potent cytotoxin and chymotrypsin inhibitor from the marine cyanobacterium Symploca sp
Journal of Natural Products, 2008Co-Authors: Roger G Linington, Kerry L Mcphail, Daniel J Edwards, Cynthia F Shuman, Teatulohi Matainaho, William H GerwickAbstract:Investigation of a Symploca sp. from Papua New Guinea has led to the isolation of Symplocamide A (1), a potent cancer cell cytotoxin, which also inhibits serine proteases with a 200-fold greater inhibition of chymotrypsin over trypsin. The complete stereostructure of Symplocamide A was determined by detailed NMR and MS analysis as well as chiral HPLC analysis of the component amino acid residues. The presence of several unusual structural features in Symplocamide A provides new insights into the pharmacophore model for protease selectivity in this drug class and may underlie the potent cytotoxicity of this compound to H-460 lung cancer cells (IC50 = 40 nM) as well as neuro-2a neuroblastoma cells (IC50 = 29 nM).
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belamide a a new antimitotic tetrapeptide from a panamanian marine cyanobacterium
Tetrahedron Letters, 2006Co-Authors: Kerry L Mcphail, William H Gerwick, Susan L Mooberry, Luke T Simmons, Eduardo OrtegabarriaAbstract:Abstract The isolation and structure elucidation of belamide A from the marine cyanobacterium Symploca sp. is described. Belamide A is a highly methylated linear tetrapeptide with structural analogy to the important linear peptides dolastatins 10 and 15. Disruption of the microtubule network in A-10 cells was observed at 20 μM and displayed classic tubulin destabilizing antimitotic characteristics. The moderate cytotoxicity of belamide A (IC 50 0.74 μM vs HCT-116 colon cancer line) provides new insights into structure–activity relationships for this drug class.
