Tunicates cells

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. 

Hirose, E. (1999) Pigmentation and add storage in the tunic protective functions of the tunic cells in the tropical asddian Phallusia nigra. Invertebr. Biol., 118,414-422. 

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 Unfortunately, no favorable responses were found so the compound has been withdrawn.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... 

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. 

Tunicates (ascidians or sea-squirts) are invertebrate marine organisms, which can accumulate vanadium at concentrations approaching 350 mM (the concentration of vanadium in seawater is 10 8 M). This vanadium is taken up as V(V) from seawater (Figure 17.16), reduced to oxidation state III or IV and stored in a soluble form in the blood cells within acidic vacuoles at concentrations a million fold higher than in their external surroundings. 

The pyridoacridine alkaloids, kuanoniamines A-D (133-136) were isolated from an unidentified Micronesian tunicate and its nudibranch predator, Chelynotus semperi. The structures were established by extensive NMR spectral analysis. Cytotoxicity against KB cells ranged from IC50 values >10 ig/mL for kuanoniamine B (134), 5 ig/mL for kuanoniamine D (136), to 1 ig/mL for kuanoniamine A (133) [145]. Kuanoniamine A (133) has also been synthesised [146,147]. 

The Mediterranean tunicate Sidnyum turbinatum contained four alkyl sulfates, 1-heptadecanyl sulfate (167), 1-octadecanyl sulfate (168), sodium (2S)-2,6,10,14-tetramethylpentadeca-1,18-diyl sulfate (169) and 1-hexyl sulfate (170). The structures were determined by spectroscopic and chemical methods. All exhibited antiproliferative activity in vitro against the murine fibrosarcoma cell line, WEHI164 [166]. 

The sea squirts or tunicates are fascinating marine creatures, their name being derived from the tunic made of cellulosic material that surrounds the body of the animal. In 1911, Henze discovered vanadium in the blood of Phallusia mammillata C.343 He later found the same with other ascidians (a class of tunicates). In vanadium-accumulating species, most vanadium is located in the vacuoles—vanadophores—of certain types of blood cells—the vanadocytes. The concentration in the vanadophore can be as high as 1M and this value must be compared with concentrations of the order of 2 x 10-8 M for vanadium in sea water.344 Kustin et al. have reviewed the work done to understand the efficient accumulation and the possible biological roles of the metal.345... 

The first suggestion of a possible biochemical function for vanadium came from the discovery that vanadocytes, the green blood cells of tunicates (sea squirts), contain 1.0 M V(III) and 1.5-2 M H2S04. 613 It was proposed that a V-containing protein is an oxygen carrier. However, the V3+ appears not to be associated with proteins612 and it does not carry 02. 

Meridianins, brominated indole alkaloids from the tunicate Aplidium meridianum, show cytotoxicity against LMM3 (murine mamarian adenocarcinoma cell line) with IC5o values of 11.4 jM for meridianin B (25), 9.3 iM for meridianin C (26), 33.9 iM for meridianin D (27), and 11.1 aM for meridianin E (28) [41]. 

The didemnolines A-D (30-33) isolated from the tunicate Didemnum sp. represent an additional family of P-carboline metabolites [33]. They differ from the other derived P-carboline compounds in that they are substituted at the N9 position rather than at the C-l position. All of these compounds showed moderate cytotoxic activity against KB cells, with the sulfoxide-containing compound, didemnoline C (32), being the most active with an IC50 value of 0.28 pg/ml. Compounds 30 and 32 also exhibited... 

Thiazole-containing linear peptides have also been isolated from tunicates. Virenamides A-E (412-416) were obtained from the didemnid tunicate Diplosoma virens, which contains symbiotic prokaryotic algae in its cloacal cavity. The structures of virenamides A-C were determined by HPLC analysis using Marfey s procedure [323] while the absolute stereochemistry of virenamide E (416) was proven by its synthesis from virenamide A (412) [324], Compounds 412-416 showed modest cytotoxicity toward a panel of cultured cells and 412 also exhibited topoisomerase II inhibitory activity. 

A series of macrolides bearing a thiazole moiety have been isolated from tunicates and sponges. The tunicate Lissoclinum patella has afforded the patellazoles A-C (428-430), which were found to be potent cytotoxins in the NCI human cell line protocol with mean IC50 values of 10-3—10-6 pg/ml as well as exhibiting antifungal activity [334, 335]. Furthermore, patellazole B (429) exhibited very potent antiviral activity against Herpes symplex viruses [334],... 

The ascidians or tunicates (sea squirts) accumulate vanadium from seawater (about 5x 10-8 mol dm-3) to a level of about 1 mol dm-3 and store it in a dilute solution of sulfuric acid (pH<2) in blood cells called vanadocytes. The tunicates thus concentrate vanadium several million-fold. 079 NMR, ESR and EXAFS determinations on whole vanadocyte cells of Ascidia ceratodes and Ascidia nigra indicate that the vanadium is present mainly as aquated V111 probably complexed with sulfate. Some vanadyl ion (5-10%) is also present.1080 1081... 

Grossularins I (37) and II (38), the first examples of naturally occurring a-carbolines, were obtained from a French solitary tunicate (Dendrodoa grossularia) and were found to be cytotoxic toward L1210 leukemia cells (55). Previously the structure of grossularin I was proposed as 39 (56), which was revised to 37 on the basis of comparison with the structure of grossularin II (38). Structural proof for 38 was unambiguously provided by X-ray analysis. The same tunicate contained 3-indolyl-4//-imidazol-4-one (40), the structure of which was confirmed by synthesis (57). The imidazo-lone compound (40) was devoid of cytotoxicity. 

The Okinawan tunicate Eudistoma cf. rigida contained novel nitrogen-containing macrolides, namely, iejimalides A (276) and B (277) which show potent cytotoxicity against murine leukemia cells (227). Iejimalides possess a unique structure with AMormyl-L-serine in the side chain and are the first macrolides isolated from a tunicate. 

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