2. Academic Validation
  3. Leucettamol A: a new inhibitor of Ubc13-Uev1A interaction isolated from a marine sponge, Leucetta aff. microrhaphis

Leucettamol A: a new inhibitor of Ubc13-Uev1A interaction isolated from a marine sponge, Leucetta aff. microrhaphis

  • Bioorg Med Chem Lett. 2008 Dec 15;18(24):6319-20. doi: 10.1016/j.bmcl.2008.10.110.
Sachiko Tsukamoto 1,  Tomoharu Takeuchi,  Henki Rotinsulu,  Remy E P Mangindaan,  Rob W M van Soest,  Kazuyo Ukai,  Hisayoshi Kobayashi,  Michio Namikoshi,  Tomihisa Ohta,  Hideyoshi Yokosawa
Affiliations

Affiliation

  • 1 Graduate School of Science, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan. sachiko@faculty.chiba-u.jp
PMID: 19006668 DOI: 10.1016/j.bmcl.2008.10.110
Abstract

A compound that inhibits the formation of a complex composed of the ubiquitin E2 Enzyme Ubc13 and Uev1A was isolated from the marine Sponge Leucetta aff. microrhaphis. The compound was identified as leucettamol A (1) by spectroscopic analysis. Its inhibition of Ubc13-Uev1A interaction was tested by the ELISA method, revealing an IC(50) value of 50 microg/mL. The compound is the first inhibitor of Ubc13-Uev1A interaction, that is, that of the E2 activity of Ubc13. Such inhibitors are presumed to be leads for anti-cancer agents that upregulate activity of the tumor suppressor p53 protein. Interestingly, hydrogenation of 1 increased its inhibitory activity with an IC(50) value of 4 microg/mL, while its tetraacetate derivative was inactive, indicating that the hydroxy and/or amino groups of 1 are required for the inhibition.

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