Dolabella

In contrast, jasplakinolide, a cyclodepsipeptide from the marine sponge Jaspis johnstoni, rapidly penetrates the cell membrane. It competes with phalloidin for F-actin binding and has a dissociation constant of approximately 15 nM. It induces actin polymerization and stabilizes pre-existing actin filaments. Dolastatin 11, a depsipeptide from the mollusk Dolabella auricu-laria, induces F-actin polymerization. Its binding site differs from that of phalloidin or jasplakinolide. 

A saponin-like substance, agelasine, was isolated from Agelas dispar (10). Suber-itine from Suberites domcunculus was originally isolated by Richet (32) and was shown to be heat labile and have a MW of 28,000 by Cariello et al. (33). A cyclic peptide, dolastin, was isolated from Dolabella awicularia (34). 

Extract and caulerpenyne from Guam specimens inhibit feeding by the mollusk Dolabella auricularia (Pennings and Paul 1992)... 

Bai R, Friedman SJ, Pettit GR, Hamel E. (1992) Dolastatin 15, a potent antimitotic depsipeptide derived from Dolabella auricularia. Interaction with tubulin and effects of cellular microtubules. Biochem Pharmacol 43 2637-2645. 

Scheme 14 Final steps toward the total synthesis of (-)-palominol (49) and (-i-)-dolabella-trienone (47) (2003)...

Marine organisms represent a largely unexplored source of unique toxic chemicals. These toxins are produced by the organisms as defense weapons against their predators. Several potent compounds demonstrating antitumor activity in vitro and in vivo have been isolated from marine organisms, e. g., the bryostatins (from Bugula neritina), dolastin 10 (from Dolabella auricularia) and halichondrine B (from Halichondria okadat) [61]. 

Dolabella auricularia). Another prominent family of peptides has also been isolated from mollusks these highly compact and stable linear peptides, known as conotoxins, exhibit specific actions on the ion channels and membrane receptors of excitable cells. 

FIGURE 5.1 Structure of dolastatin 10 derived from the sea hare (mollusk) Dolabella auricularia. 

The antineoplastic, cyclic peptide dolastatin 3 (197) was isolated from the sea hare Dolabella auricularia in small quantities [187]. It bears much structural resemblance to the cyclic peptides of tunicates. Synthetic attempts indicated that the original published structure was incorrect [188]. Three reports of research directed towards synthesis of possible components of dolastatin 3 (197) failed to help with the correct structure [189-191]. Reisolation of 197 allowed the determination of the correct sequence of amino acids in this cyclic pentapeptide and the new structure was confirmed by synthesis [192]. Synthesis of dolastatin 3 (197) and the corresponding 12R diastereoisomer permitted study of the solution... 

These polyketides, plakortides, have also been shown as potent activators of cardiac calcium-pumping ATPase [434], New cyclic polyketides were recently isolated from the Red Sea marine sponge Acarnus bergquistae [435], while cytotoxic polyketides have also been reported from sea hares of the genus Aplysia and Dolabella [436], and the marine sponge The one Ha swinhei [437],... 

The macrolide glycosides, aurisides A (17) and B (18), from the Japanese sea hare Dolabella auricularia show cytotoxicity against HeLa S3 cells with IC50 values of 0.17 and 1.2 pg/ml, respectively [35]. 

The bromotriterpene aurilol (19) also was isolated from the sea hare Dolabella auricularia. Aurilol exhibits cytotoxicity against HeLa S3 cells with an IC50 of 4.3 pg/ml [36]. 

Dolabellin (169), a bisthiazole metabolite from the Japanese sea hare Dolabella auricularia containing 7,7-dichloro-octanoic acid, shows cytotoxicity against HeLa S3 cells (IC5o 6.1 pg/ml). The dechloro analogue has only one third of the toxicity [130]. 

The thiazoline and thiazole rings are present in many cyclic peptides isolated from marine organisms. Most of these types of compound have been isolated from tunicates belonging to the Lissoclinum and Didemnum genus, from sponges of the genus Theonella, and from the sea hare mollusc Dolabella auricularia. The isolation of closely related compounds from cyanobacteria pointed out the symbiont origin of these metabolites. 

The sea hare Dolabella auricularia has been the source of the powerful cytotastic and antineoplastic constituents designated as dolastatins [311]. Some of these compounds are thiazole-containing cyclic peptides. They were found in very small quantities in the animal (ca. 1 mg each from 100 Kg), making the isolation and structural elucidation of these peptides exceptionally challenging. A review on the dolastatins, written by G. R. Pettit in 1997, covers the reported literature regarding their isolation, characterization, biological activity, and synthesis [312]. Pettit and coworkers reported the thiazole-containing dolastatins dolastatin 3 (404) [313], 10 (2) [314], and 18 (407) [315]. The most important dolastatin and the most potent antineoplastic and tubulin-inhibitory substance known to date is the unique linear pentapeptide dolastatin 10 (2). 

This review describes the chemistry of the bioactive compounds isolated from the sea hares belonging to two genera Aplysia and Dolabella Yamada, K. Kigoshi, H. Bull. Chem. Soc. Jpn., 1997, 70, 1479-1489. 

The sea hare Dolabella auricularia has furnished aurilol (628), which is cytotoxic (728) and for which the structure has now been fully assigned by total synthesis (729). The Indian Ocean red alga Chondria armata, a member of the Laurencia family, contains armatols A-F (629-634) (730). 

Several other, more complex cysteine-derived polychlorinated peptide metabolites are known to arise in marine organisms. Dolabellin (968) was characterized from the Japanese sea hare Dolabella auricularia 1004). The absolute... 

Yamada K, Kigoshi H (1997) Bioactive Compounds from the Sea Hares of Two Genera Aplysia and Dolabella. Bull Chem Soc Jpn 70 1479... 

Suenaga K, Shibata T, Takada N, Kigoshi H, Yamada K (1998) Aurilol, a Cytotoxic Bromotriterpene Isolated from the Sea Hare Dolabella auricularia. J Nat Prod 61 515... 

Sone H, Kondo T, Kiryu M, Ishiwata H, Ojika M, Yamada K (1995) Dolabellin, a Cytotoxic Bisthiazole Metabolite from the Sea Hare Dolabella auricularia Structural Determination and Synthesis. J Org Chem 60 4774... 

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