DICTYOSTATIN

Source: Unidentified Jamaican sponge of Family Corallistidae (PORIFERA)
Activity: tubulin interactive compound
Status: Preclinical

Dictyostatin was first isolated in 1994 by Bob Pettit and his colleagues at Arizona State University from a sample of an unidntified dictyoceratid sponge of genus Spongia collected in Jamaica.

The compound was later isolated from from a lithistid sponge of the family Corallistidae and has been more fully repurified and characterized by researchers at Harbor Branch Oceanographic Institution and elsewhere.

Dictyostatin inhibits the growth of human cancer cells and has been shown active against certain Taxol-resistant tumors. Its mechanism of action appears to be prevention of the breakdown of tubulin during mitosis in a fashion similar to the successful cancer drug Taxol.

Ian Patterson at Cambridge, in collaboration with Harbor Branch, has developed a synthesis method for dictyostatin, a 22-membered lactone with 11 stereocenters. In otther recent research, dictyostatin has also been syntthetically hybridized with the compound discodermolide.

NCBI PubMed biomedical literature citations and abstracts - [ LINK ]

References

Isbrucker RA, Cummins J, Pomponi SA, Longley RE, and AE Wright. 2003. Tubulin polymerizing activity of dictyostatin-1, a polyketide of marine sponge origin. Biochem Pharmacol 66:75-82.

Madiraju C, Edler MC, Hamel E, Raccor BS, Balachandran R, Zhu G, Giuliano KA, Vogt A, Shin Y, Fournier JH, Fukui Y, Bruckner AM, Curran DP, and BW Day. 2005. Tubulin assembly, taxoid site binding, and cellular effects of the microtubule-stabilizing agent dictyostatin. Biochemistry 44:15053-15063.

Paterson I, Britton R, Delgado O, and AE Wright. 2004. Stereochemical Determination of dictyostatin-1, a Novel Microtubule Stabilizing macrolide from the Marine Sponge Corallistidae. Chem Commun 21:632-633.

Shin Y, Choy N, Turner TR, Balachandran R, Madiraju C, Day BW, and DP Curran. 2003. Discodermolide/Dictyostatin hybrids: synthesis and biological evaluation. Org Lett 12:4443-4446.

Shin Y, Fournier JH, Fukui Y, Bruckner AM, and DP Curran. 2004. Total synthesis and configurational assignment of (-)-dictyostatin, a microtubule-stabilizing macrolide of marine sponge origin. Angew Chem Int Ed (Engl) 43:4629-4633.