Dolabellin, a Cytotoxic Bisthiazole Metabolite from the Sea Hare Dolabella auricularia: Structural Determination and Synthesis

Sone, Hirohito; Kondo, Takashi; Minoru, Kiryu; Ishiwata, Hiroyuki; Ojika, Makoto; Yamada, Kiyoyuki

doi:10.1021/jo00120a021

Cited by 85 publications

(65 citation statements)

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“…Guamanian collections of L. majuscula afforded lyngbyabellins A (37) [60] and B (38) [61], close structural, cyclic analogues of the cytotoxic bisthiazole metabolite dolabellin (39) originally isolated from D. auricularia [62]. Lyngbyabellin B (38) was simultaneously reported from a Caribbean collection of L. majuscula [63].…”

Section: Other Sea Hare Isolates Of Postulated Cyanobacterial Originmentioning

confidence: 99%

The Cyanobacterial Origin of Potent Anticancer Agents Originally Isolated from Sea Hares

Luesch¹,

Harrigan²,

Goetz³

et al. 2002

CMC

133

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It is increasingly evident that the true biological origin of many metabolites originally isolated from certain marine macroorganisms is cyanobacterial. For example, several dolastatins, potent cytotoxic compounds originally derived from the sea hare Dolabella auricularia, have now been isolated from marine cyanobacteria of the genera Lyngbya and Symploca. This review discusses the isolation of dolastatins and close structural analogues from cyanobacteria. Biosynthetic signatures of metabolites isolated from sea hares, but which are most probably cyanobacterial in origin, are also presented. Finally, some more complex ecology involving movement of cyanobacterial metabolites through the marine food web is presented.

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Section: Other Sea Hare Isolates Of Postulated Cyanobacterial Originmentioning

confidence: 99%

The Cyanobacterial Origin of Potent Anticancer Agents Originally Isolated from Sea Hares

Luesch¹,

Harrigan²,

Goetz³

et al. 2002

CMC

133

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“…The assignment was corroborated by comparison with 13 C and 1 H, 13 C HSQC spectra of hexanoic acid, 5-oxo-hexanoic acid, 6-chloro-hexanoic acid, and published values for 5,5-dichlorohexanal. [19] For semiquantitative analysis of the relative amounts of the individual free products, 13 C spectra with long relaxation delays (5 s) were recorded; intensity comparisons were performed only for signals of the same multiplicity. From these, the amount of hexanoyl substrate was determined to be approximately 10 %, thus indicating almost quantitative conversion.…”

Section: Catalytic Promiscuitymentioning

confidence: 99%

More than just a Halogenase: Modification of Fatty Acyl Moieties by a Trifunctional Metal Enzyme

Pratter¹,

Ivkovic²,

Birner‐Gruenberger³

et al. 2014

ChemBioChem

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The highly selective oxidative halogenations by non-heme iron and α-ketoglutarate-dependent enzymes are key reactions in the biosynthesis of lipopeptides, and often bestow valuable bioactivity to the metabolites. Here we present the first biochemical characterization of a putative fatty acyl halogenase, HctB, which is found in the hectochlorin biosynthetic pathway of Lyngbya majuscula. Its unprecedented three-domain structure, which includes an acyl carrier protein domain, allows self-contained conversion of the covalently tethered hexanoyl substrate. Structural analysis of the native product by (13) C NMR reveals high regioselectivity but considerable catalytic promiscuity. This challenges the classification of HctB as a primary halogenase: along with the proposed dichlorination, HctB performs oxygenation and an unprecedented introduction of a vinyl-chloride moiety into the nonactivated carbon chain. The relaxed substrate specificity is discussed with reference to a molecular model of the enzyme-substrate complex. The results suggest that fatty acyl transformation at the metal center of HctB can bring about considerable structural diversity in the biosynthesis of lipopeptides.

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“…33.19). Its structure was elucidated by spectral analysis and subsequent asymmetric synthesis [168]. Dolabellin showed moderate cytotoxicity against HeLa S3 cells (IC 50 6.1 µg/mL).…”

Section: Peptides and Depsipeptidesmentioning

confidence: 99%

Antitumor Effects of Sea Hare-Derived Compounds in Cancer

Kigoshi

Kita

2014

Handbook of Anticancer Drugs From Marine Origin

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Sea hares (family Aplysiidae) are a rich source of bioactive substances. Especially, over the past 40 years, the genera Aplysia and Dolabella have afforded numerous bioactive secondary metabolites that exhibit antitumor activity. For example, the depsipeptide dolastatin 10 and its analogue are currently in cancer clinical trials. Meanwhile, the chemical probe approach has revealed that the antitumor macrolide aplyronine A inhibits microtubule assembly in association with actin. This article highlights the recent findings regarding the chemical biology of antitumor and antineoplastic compounds from sea hares, as well as molecules that have been discovered and characterized after 2000.Keywords Antitumor · Sea hare · Aplysia · Antitumor · Actin-deplymerization · Cytotoxicity · Tubulin IntroductionSea hares, which belong to the opisthobranch group of mollusks (clade Aplysiomorpha), are shell-less, slow-moving benthic marine mollusks [1]. The order Anaspidea includes two families, Akeridae and Aplysiidae [2]. Almost all chemical studies have focused on Aplysiidae specimens. The family Aplysiidae includes nine genera, Aplysia (Linnaeus 1767), Bursatella (Blainville 1817), Dolabella (Lamarck 1801), Dolabrifera (Gray 1847), Notarchus (Cuvier 1817), Petalifera (Gray 1847), Phyllaplysia (Fischer 1872), Syphonota (Adams 1854), and Stylocheilus (Gould 1852). Sea hares are herbivorous, and are typically found on seaweed in shallow water. They are not eaten by other marine animals and have been postulated to contain chemical defense substances. The poisonous properties of sea hare secretions were known in Roman times. In addition, sea hares release ink from their ink glands, which deter predators. This ink acts as a screen, while at the

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Dolabellin, a Cytotoxic Bisthiazole Metabolite from the Sea Hare Dolabella auricularia: Structural Determination and Synthesis

Cited by 85 publications

References 0 publications

The Cyanobacterial Origin of Potent Anticancer Agents Originally Isolated from Sea Hares

The Cyanobacterial Origin of Potent Anticancer Agents Originally Isolated from Sea Hares

More than just a Halogenase: Modification of Fatty Acyl Moieties by a Trifunctional Metal Enzyme

Antitumor Effects of Sea Hare-Derived Compounds in Cancer

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