Aurilide, a cytotoxic depsipeptide from the sea hare Dolabella auricularia: isolation, structure determination, synthesis, and biological activity

Suenaga, Kiyotake; Mutou, Tsuyoshi; Shibata, Toshihiro; Itoh, Takashi; Fujita, Takayoshi; Takada, Noboru; Hayamizu, Kozue; Takagi, M.; Irifune, Taiji; Kigoshi, Hideo; Yamada, Kiyoyuki

doi:10.1016/j.tet.2004.06.125

Cited by 77 publications

(54 citation statements)

References 49 publications

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“…Finally, we tried to synthesize a tetrapeptide moiety of the depsipeptidic natural product auliride ( 13 )[9] to extend the range of applications for our established process. Tetrapeptide contains two N -methyl amino acids (Scheme 2).…”

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confidence: 99%

Efficient Amide Bond Formation through a Rapid and Strong Activation of Carboxylic Acids in a Microflow Reactor

2013

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The development of highly efficient amide bond forming methods which are devoid of side reactions, including epimerization, is important, and such a method is described herein and is based on the concept of rapid and strong activation of carboxylic acids. Various carboxylic acids are rapidly (0.5 s) converted into highly active species, derived from the inexpensive and less-toxic solid triphosgene, and then rapidly (4.3 s) reacted with various amines to afford the desired peptides in high yields (74 %–quant.) without significant epimerization (≤3 %). Our process can be carried out at ambient temperature, and only CO2 and HCl salts of diisopropylethyl amine are generated. In the long history of peptide synthesis, a significant number of active coupling reagents have been abandoned because the highly active electrophilic species generated are usually susceptible to side reactions such as epimerization. The concept presented herein should renew interest in the use of these reagents.

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confidence: 99%

Efficient Amide Bond Formation through a Rapid and Strong Activation of Carboxylic Acids in a Microflow Reactor

2013

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“…It belongs to the mixed polyketide-polypeptide structural class and consists of five amino acids (Val, NMe-d-Leu, N-Me-Gly, Val, and N-Me-Ala), allo-d-isoleucic acid, and a unique extended polyketide moiety. Its absolute stereochemistry was confirmed by analysis of its hydrolysis products and enantioselective synthesis [142,143]. This molecule induces apoptosis to result in a potent antiproliferative effect against human cancer cells at the pM to nM range (e.g., IC 50 11 ng/mL against HeLa S3 cells).…”

Section: Peptides and Depsipeptidesmentioning

confidence: 91%

“…This molecule induces apoptosis to result in a potent antiproliferative effect against human cancer cells at the pM to nM range (e.g., IC 50 11 ng/mL against HeLa S3 cells). In the NCI human cancer cell panel, aurilide showed a high level of cytotoxicity (mean panel GI 50 0.12 µg/mL), and was selectively active against lung, ovarian, renal and prostate cancer cell lines [143]. Aurilide showed unusually high in vivo antitumor activity in the NCI's hollow-fiber assays, and is expected to be a promising candidate for cancer treatment.…”

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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“…27.4) and related compounds, such as the lagunamides, are potent cytotoxic cyclic depsipeptides having activities in the pico to nanomolar range. Similar to the dolastatins, aurilide was first isolated from the Japanese sea hare, Dolabella auricularia [52,53]. However, the microbial biogenesis of this molecule is implicated due to reports of related analogs purified from marine cyanobacterial strains [54].…”

Section: Aurilides/lagunamidesmentioning

confidence: 99%

Molecular Targets of Anticancer Agents from Filamentous Marine Cyanobacteria

Tan

Gupta

2014

Handbook of Anticancer Drugs From Marine Origin

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The prokaryotic marine cyanobacteria, especially the filamentous forms, are known to produce a plethora of structurally unique natural products. A majority of these molecules are nitrogen-containing, belonging to the hybrid polyketide-polypeptide structural class. Various activities of clinical significance have been attributed to these molecules, ranging from anticancer, neuromodulating to antiprotozoal properties. Particularly in the area of cancer therapy, a number of potent marine cyanobacterial compounds, including dolastatins 10, 15, and largazole, have been identified as anticancer drug leads and are being further developed synthetically for clinical usage. The high potencies of these compounds are due to their exquisite interactions or interference with cellular pathways, specific macromolecules, or enzymes, such as the JAK-STAT signaling pathway, histone deacetylase, proteasome, protein kinase C, actin and microtubule filaments. This mini review covers more than 90 references and features more than 40 anticancer compounds, consisting of marine cyanobacterial natural products and their synthetic analogues. Biological data of these compounds are discussed based on their molecular targets.

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Aurilide, a cytotoxic depsipeptide from the sea hare Dolabella auricularia: isolation, structure determination, synthesis, and biological activity

Cited by 77 publications

References 49 publications

Efficient Amide Bond Formation through a Rapid and Strong Activation of Carboxylic Acids in a Microflow Reactor

Efficient Amide Bond Formation through a Rapid and Strong Activation of Carboxylic Acids in a Microflow Reactor

Antitumor Effects of Sea Hare-Derived Compounds in Cancer

Molecular Targets of Anticancer Agents from Filamentous Marine Cyanobacteria

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