Leucettamol A: a new inhibitor of Ubc13-Uev1A interaction isolated from a marine sponge, Leucetta aff. microrhaphis.
Basic Information
ID: ALA1152207
Journal: Bioorg Med Chem Lett
Title: Leucettamol A: a new inhibitor of Ubc13-Uev1A interaction isolated from a marine sponge, Leucetta aff. microrhaphis.
Authors: Tsukamoto S, Takeuchi T, Rotinsulu H, Mangindaan RE, van Soest RW, Ukai K, Kobayashi H, Namikoshi M, Ohta T, Yokosawa H.
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.
CiteXplore: 19006668
DOI: 10.1016/j.bmcl.2008.10.110
Patent ID: ┄