Parallel synthesis and yeast growth inhibition screening of succinamic acid libraries

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.