Parallel synthesis and yeast growth inhibition screening of succinamic acid libraries

J Comb Chem. 2007 Jul-Aug;9(4):635-43. doi: 10.1021/cc070026n. Epub 2007 May 31.

Abstract

Libraries of succinamic acid derivatives resulting from the condensation of a series of succinic acid derivatives with amines are reported as putative khafrefungin analogues. A total of 480 compounds derived from the initial condensation of 8 scaffolds with 60 different amines have been synthesized using automated technology with the help of scavenger resins. A simple acetate hydrolysis of five of the above sublibraries afforded additional 300 compounds for a total of 780 compounds. Around 55% of the library members showed purities higher than 70% (HPLC-ELS-MS) thus proving the generality of this approach. Results on growth inhibition of the yeast Saccharomyces cerevisiae in the presence of selected library members are also reported as a preliminary evaluation of the antifungal activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Amines / chemistry
  • Anhydrides / chemistry
  • Animals
  • Antifungal Agents / chemical synthesis*
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Databases, Factual*
  • Drug Evaluation, Preclinical
  • Glycolipids / chemistry
  • Molecular Structure
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / drug effects*
  • Sphingolipids / biosynthesis
  • Sphingolipids / chemistry
  • Succinic Acid / chemistry*
  • Succinic Acid / pharmacology*

Substances

  • Amines
  • Anhydrides
  • Antifungal Agents
  • Glycolipids
  • Sphingolipids
  • khafrefungin
  • Succinic Acid