A Tale from the Sea to Ara C

. . . what sponges have to do with saving the lives of children with ALL

Spongistatin 1 is another compound isolated from marine sponges that might enter the arsenal of anti-cancer drugs. It is not similar in structure to Ara C, Ara G, or Clofarabine, but to me, it is still interesting because it is isolated from sponges. It is a macrocyclic lactone polyether - not a nucleoside like the other compounds discussed in this essay. It's a large molecule, and I don't feel like trying to draw it out in ChemDraw, so I'll just give this reference for the structure.

The first literature reference for spongistain 1 is an article in Molecular Pharmacology published in 1993 (1). I can't get the full text of the article, so I don't know how or why they first decided to isolate this molecule from a Spongia species. They report that it inhibit mitosis in murine leukemia cells in culture.

In 2008, an article in Leukemia (2) reports that spongistatin is quite promising as a chemotherapy agent because it induces apoptosis in Jurkat leukemia T cells and, more importantly, in primary leukemia cells.

As of 2011, Spongistatin is still of interest in anti-cancer research. (3, 4)

(1) Spongistatin-1, a highly cytotoxic, sponge-derived, marine natural product that inhibits mitosis, microtubule assembly, and the binding of vinblastine to tubulin. RL Bai et al., Molecular Pharmacology, Volume 44, Issue 4, pp. 757-766, 1993.

(2) Spongistatin 1: a new chemosensitizing marine compound that degrades XIAP. L Schyschka, A Rudy, I Jeremias, N Barth, G R Pettit and A M Vollmar, Leukemia, September 2008 Volume 22 Number 9, pp 1651 - 1812.

(3) In Vitro and In Vivo Anticancer Activity of (+)-Spongistatin 1. Xu Q et al., Anticancer Res. 2011 Sep;31(9):2773-2779.

(4) Drugs that target dynamic microtubules: a new molecular perspective. Stanton RA et al., Med Res Rev. 2011 May;31(3):443-81.

Patty, August 2011

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