Polyacetylenes inhibitors

The involvement of desaturase-type enzymes in the biosynthesis of some important lipidic antifeedants now has been firmly established (Fig. Ic) (7). An instructive example of this phenomenon is the production of ricinoleate (a purgative) by a desaturase homolog found in the castor plant. Here, a subtle variation in mechanistic pathway is responsible for the introduction of a C-12 hydroxyl group rather than a 12,13-double bond (7). Another interesting case features the putative dehydrogenation of a cyclopropyl fatty acid to produce sterculate, a potent inhibitor of the mammalian but not the plant A desaturase (8). Finally, the biosynthesis of polyacetylenes with antifungal properties such as falcarindiol is thought to involve a sequence of unique desaturase-mediated oxidations (9). 

The petroleum ether extract of Panax ginseng has antiproliferative effects on various cancer cell lines (murine sarcoma, murine leukaemia, human colon carcinoma, etc ). Polyacetylenic compounds from this extract such as panaxynol, panaxydol (46) and panaxytriol have been reported to be responsible for these effects [112, 113]. In order to identify the molecular mechanism of the polyacetylene compounds, one of the major cytotoxic compounds, panaxydol, was examined to see if it is able to disrupt cell cycle-related events. It was observed that panaxydol induces cell cycle arrest at Gi-S transition in SK-MEL-1 cells. This effect is related to the decreased Cdk2 activity, which seems to be caused by the increased level of p27 protein expression. The protein synthesis inhibitor cycloheximide reversed the growth suppression induced by panaxydol (80 j,g/ml) by... 

Patil, A.D. Kokke, W.C. Cochran, S. Francis, T.A. Tomszek, T. Westley, J.W. Brominated Polyacetylenic Avids from The Marine Sponge Xestospongia muta Inhibitors of HIV Protease. J. Nat. Prod. 1992,55, 1170-1177. 

Fusetani, N., Y. Kato, S. Matsunaga, and K. Hashimoto Bioactive Marine Metabolites III. A Novel Polyacetylene Alcohol, Inhibitor of Cell Division in Fertilized Sea Urchin Eggs, from the Marine Sponge Tetrosia sp. Tetrahedron Lett. 24, 2771 (1983). 

Nishimura, S., Matsunaga, S., Shibazaki, M., Suzuki, K Harada, N., Naoki, H., and Fusetani, N. (2002) Corticatic acids D and E, polyacetylenic geranylgeranyltransferase type 1 inhibitors, from the marine sponge Petrosia corticata. J. Nat. Prod., 65,1353-1356. 

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