Kulokekahilide-2, a Cytotoxic Depsipeptide from a Cephalaspidean Mollusk <i>Philinopsis speciosa</i>

Nakao, Yoichi; Yoshida, Wesley Y.; Takada, Yuuki; Kimura, Junji; Liu, Yang; Mooberry, Susan L.; Scheuer, Paul J.

doi:10.1021/np049949f

Cited by 78 publications

(69 citation statements)

References 34 publications

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“…These compounds belong to the mixed polyketide-polypeptide structural class, consisting of five amino acids (Ala, N Me-Phe, N Me-Gly, Ile, and N Me-Ala), one-hydroxy acid (2-hydroxy-isoleucic acid) and a unique extended polyketide moiety. The lagunamides are structurally related to the aurilide class of molecules, which include aurilides B ( 4 ) and C ( 5 ) and kulokekahilide-2 ( 6 ) (Chart 1) [13,14,15]. Aurilide ( 3 ), the first member of this class of molecules, was originally reported from the sea hare, Dolabella auricularia [16].…”

Section: Resultsmentioning

confidence: 99%

Biochemical Studies of the Lagunamides, Potent Cytotoxic Cyclic Depsipeptides from the Marine Cyanobacterium Lyngbya majuscula

et al. 2012

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Lagunamides A (1) and B (2) are potent cytotoxic cyclic depsipeptides isolated from the filamentous marine cyanobacterium, Lyngbya majuscula, from Pulau Hantu, Singapore. These compounds are structurally related to the aurilide-class of molecules, which have been reported to possess exquisite antiproliferative activities against cancer cells. The present study presents preliminary findings on the selectivity of lagunamides against various cancer cell lines as well as their mechanism of action by studying their effects on programmed cell death or apoptosis. Lagunamide A exhibited a selective growth inhibitory activity against a panel of cancer cell lines, including P388, A549, PC3, HCT8, and SK-OV3 cells, with IC50 values ranging from 1.6 nM to 6.4 nM. Morphological studies showed blebbing at the surface of cancer cells as well as cell shrinkage accompanied by loss of contact with the substratum and neighboring cells. Biochemical studies using HCT8 and MCF7 cancer cells suggested that the cytotoxic effect of 1 and 2 might act via induction of mitochondrial mediated apoptosis. Data presented in this study warrants further investigation on the mode of action and underscores the importance of the lagunamides as potential anticancer agents.

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Section: Resultsmentioning

confidence: 99%

Biochemical Studies of the Lagunamides, Potent Cytotoxic Cyclic Depsipeptides from the Marine Cyanobacterium Lyngbya majuscula

et al. 2012

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“…Kulokekahilide-2 (82) (Fig. 9) is another potent auriliderelated compound initially isolated from the Hawaiian marine mollusk, Philinopsis speciosa (Nakao et al 2004). It is hypothesized that kulokekahilide-2 is biosynthesized by marine cyanobacteria due to its close structural similarities with the aurilides.…”

Section: Aurilides and Analoguesmentioning

confidence: 99%

Filamentous tropical marine cyanobacteria: a rich source of natural products for anticancer drug discovery

2010

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“…As with aurilide, aurilides B and C showed significant in vivo antitumor activities based on NCI's hollow fiber assay. Kulokekahilide-2, a cytotoxin that is structurally related to aurilide, was isolated from the Hawaiian cephalaspidean mollusk Philinopsis speciosa [148,149]. The total synthesis of kulokekahilide-2 was completed, and SAR studies revealed that the chirality at the l-Ala and N-Me-d-Phe residues is essential for its potent cytotoxicity [150].…”

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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Kulokekahilide-2, a Cytotoxic Depsipeptide from a Cephalaspidean Mollusk Philinopsis speciosa

Cited by 78 publications

References 34 publications

Biochemical Studies of the Lagunamides, Potent Cytotoxic Cyclic Depsipeptides from the Marine Cyanobacterium Lyngbya majuscula

Biochemical Studies of the Lagunamides, Potent Cytotoxic Cyclic Depsipeptides from the Marine Cyanobacterium Lyngbya majuscula

Filamentous tropical marine cyanobacteria: a rich source of natural products for anticancer drug discovery

Antitumor Effects of Sea Hare-Derived Compounds in Cancer

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