Tunicate

1 Natural History of Tunicates—Our Closest Marine Invertebrate Relations 

A protonated nitrogen, rather than an oxygen on an X-ray diagram, led to the publication of the incorrect initial chemical structure of diazonamide 

ID50 = 11ng/mL L1210 leukemia Phase II discontinued 

A number of historically significant marine natural products have established macromarines as a valuable source of physiologically active molecular scaffolds. In addition, many of the compounds illustrated in this work are currently in clinical development. Unfortunately, the journey from initial isolation to clinical development has ended for a number of notable compounds. Among the list found in Table 6.1 are leads obtained from the macromarines such as sponges, tunicates and molluscs. Although synthetic derivatives often attempt 

Clinical trial Compound name Source Target Discovering lab 

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Animal aquaculture is concentrated on finfish, moUuscs, and cmstaceans. Sponges, echinoderms, tunicates, turtles, frogs, and alligators are being cultured, but production is insignificant in comparison with the three principal groups. Common and scientific names of many of the species of the finfish, moUuscs, and cmstaceans currently under culture are presented in Table 2. Included are examples of bait, recreational, and food animals. 

The majority of promising drug candidates emerging from marine natural products research to date are potential cancer treatments. Six anti-cancer compounds that are either marine natural products or synthetic analogs of marine natural products have made it to clinical trials. The first of these compounds to enter clinical trials was didemnin B (43), one of a family of cyclic depsipetides isolated from the Caribbean tunicate Trididemnum solidum Didemnin B was advanced to Phase II clinical trials for treatment of small cell lung cancer, myeloma, prostate cancer, and melanoma. Unfortunately, no favorable responses were found so the compound has been withdrawn. Crude extracts of another Caribbean tunicate, Ecteinascidia turbinata, showed extremely... 

The 4-aryl-2(5// )-furanone unit proved to be present in many naturally occurring (91JOC6275) and medicinally important compounds (93JHC1581). Examples are the potent antibiotics rubrolide A-F 90a-f, isolated by Miao and Andersen from the colonial tunicate Ritterela rubra (Scheme 26) (91JOC6275). 

Fig. 10.S.1 The tunicate Pyrosoma atlanUcum. Photo by Herb Gruenhagcn.

Fig. 10.5.2 Bioluminescence spectrum (corrected) of the tunicate Pyrosoma atlanticum. From Herring, 1983, with permission from the Royal Society.

Chiba, K., Hoshi, M., Isobe, M., and Hirose, E. (1998). Bioluminescence in the tunic of the colonial ascidian Clavelina miniata identification of luminous cells in vitro. J. Exp. Zool. 281 546-553. 

Hirose, E., Aoki, M., and Chiba, K. (1996). Fine structures of tunic cells and distribution of bacteria in the tunic of the luminescent ascidian Clavelina miniate. Zool. Sci. 13 519-523. 

Phylum Chordata Tunicates, sharks, bony fishes, amphibians, reptiles, birds, mammals... 

Nickel exists in the tunicate Trididemnum solidum as the nickel complex of a modified chlorin (Bible et al. 1988) and is a component of a number of enzymes. Urease is the classic example of a nickel-containing enzyme, and several enzymes contain both nickel and iron. Details of enzymes that contain nickel have been provided in a review (Mulrooney and Hausinger 2003), and only brief summaries are provided ... 

Bible KC, M Buytendorp, PD Zierath, KL Rinehart (1988) Tunichlorin a nickel chlorin isolated from the Caribbean tunicate Trididemnum solidum. Proc Natl Acad Sci USA 85 4582-4586. 

Larvae of the tunicate Trididemnum solidum are most likely protected by didemnins like 44-46, cyclic depsipeptides that were initially identified from adults of this species [92]. The larvae are highly unpalatable to the wrasse Thalassoma bifasciatum, which rejected the larvae while readily consuming krill eyes that served as larval mimics. Coating one krill eye with the lipid soluble compounds from a single T. solidum larva rendered it as unpalatable as the larvae themselves. Reduced feeding was also observed when didemnin B (45) and nor-didemnin B (46) were administered to reef fishes in the field (Scheme 12) [92]. 

Scheme 12 Didemnins from the tunicate Trididemnum solidum...

Nomura and Ogata provided the first evidence that tunicates can produce PGs [17]. Using a rat stomach fundus bioassay, Halocynthia roretzi tissues were shown to possess low levels of PGs. The testes showed higher levels (9 ngg-1 wet tissue) than ovary and muscle tissue. The sea-squirt Styela clava did not show PGs by this method. No structures were determined in this work. Reexamination of the ability of H, roretzi to produce PGs was carried out by Ogata and coworkers [19]. Incubation of selected tissues with 14C-labeled eicosa-8,11,14-trienoic acid and subsequent isolation of PGE and PGF fractions after addition of carrier showed the branchial tissue to have the highest conversion levels. Quantitation was done by LSC. Using a TLC radioscanner, the authors determined that fractions with metabolites similar to PGE and PGF... 

Perry and Lambert suggest that the natural role of oxylipins in tunicates may be in the control of metabolic processes [207],... 

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