Calyculin sponge

Following the first report of tumor promotion by okadaic acid, additional tumor promoters of the okadaic acid activity class have been identified, e.g., microcystin [513,514], and calyculin derivatives, Fig. (63) reported in marine sponges such as Discodermia calyx [515] and Theonella swinhoei [516] as potent inhibitors of tumor cell proliferation. A two-sponge association, Poecillastra sp. and Jaspis sp., yielded cytotoxic toxins which exhibited selective activity against several tumoral cell lines [517],... 

The Japanese sponge Discodermia calyx has yielded the new calyculin, calyculin J (1669) (1631). The highly toxic (ichthyotoxicity, hemolytic activity) prymnesin-1 (1670) and -2 (1671), possessing unprecedented structural complexity, were characterized from the red tide alga Prymnesium parvum (1632-1634). 

Matsunaga S, Wakimoto T, Fusetani N (1997) Isolation of Four New Calyculins from the Marine Sponge Discodermia calyx. J Org Chem 62 2640... 

Calyculins A-H are bioactive metabolites isolated from the sponge Discodermia calyx Calyculins are potent serine-threonine protein phosphatase (PPl and PP2A) inhibitors and endowed with remarkable cell membrane permeability. The absolute stereochemistry of calyculins and its C33—C37 portion has been investigated. The relative configuration of the stereocenters was determined by X-ray analysis. ... 

Senecio vernalis (senecivernine), 244 Sesbania drummodii seeds (sesbanimide A and sesbanimide B), 182 Sesbania punicea (sesbanimide A and sesbanimide B), 182 sponge Discodermia calyx (calyculin),... 

The calyculins make up a family of potent, selective serine-threonine phosphatase inhibitors, which have been isolated from the Japanese sponge Discodermia calyx.There are at least 13 different members of this family, and the most abundant are calyculin A 1189a and calyculin C 1189c." As nanomolar inhibitors of protein phosphatases 1 and 2A (PPl and PP2A), 1189a and analogs have... 

Okadaic acid (OA), being a polyether, presents ionophoretic properties (facilitation of ion transport across membranes) as does CTX. It has been found that OA causes contraction in smooth muscles even in the absence of Ca (Ozaki and Karaki 1987 Shibata 1985). Ozaki and Karaki (1987) studied the mechanism of action of OA compared to calyculin A (another polyether isolated from a marine sponge). The results of this work suggest that OA has two separate effects activation of calcium channels as well as activating contractile elements to induce smooth muscle contraction. Recently, OA, in addition to other compounds from marine sources, has been found to be a tumor promoter that is, an agent that promotes tumor formation on already initiated cells (Fujiki 1988). It has been found that the OA class of tumor promoters bind to their own receptors which are present in particulate as well as cytosol fractions. The mechanism of action of these compounds has been partially elucidated. 

Calyculin A Discodermia calyx (Sponge) — Inhibitor of protein phosphatases 250/10 pg... 

Edrada, R.A., Ebel, R., Supriyono, A., Wray, V., Schupp, P., Steube, K., Van Soest, R, and Proksch, P. (2002a) Swinhoeiamide A, a new highly active calyculin derivative from the marine sponge Theondla swinhoei.]. Nat. Prod., 65, 1168-1172. 

Kato, Y, Fusetani, N., Matsunaga, S., Hashimoto, K., Fujita, S., and Furuya, T. (1986a) Calyculin A, a novel antitumor metabolite from the marine sponge Discodermia calyx. J. Am. Chem. Soc., 108, 2780-2781. 

Matsunaga, S., Fujiki, H., Sakata, D., and Fusetani, N. (1991b) Calyculins E, F, G, and H, additional inhibitors of protein phosphatases 1 and 2A, from the marine sponge Discodermia calyx. Tetrahedron, 47, 2999-3006. 

Matsunaga, S., Wakimoto, T, Fusetani, N and Suganuma, M. (1997a) Isolation of four new calyculins from the marine sponge Discodermia calyx. /. Org. Chem., 62, 2640-2642. Addition/correction J. Org. Chem., 62, 9388. 

Okada, A., Watanabe, K., Umeda, K., and Miyakado, M. (1991) Calyculin E and F, novel insecticidal metabolites from the marine sponge, Discodermia sp. Agric. Biol Chem., 55, 2765-2771. 

Dumdei, E.J., Blunt, J.W., Munro, M.H.G., and Pannell, L.K. (1997a) Isolation of calyculins, calyculinamides, and swinholide H from the New Zealand deep-water marine sponge Lamellomorpha strongylata. f Org. Chem., 62, 2636-2639. 

---