Parallel synthesis and yeast growth inhibition screening of succinamic acid libraries.
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.
Serrano
Pedro
P
Research Unit on Bioactive Molecules, Departament de Química Orgànica Biologica, Institut d'Investigacions Químiques i Ambientals de Barcelona, Jordi Girona 18-26, 08034 Barcelona, Spain.
Casas
Josefina
J
Llebaria
Amadeu
A
Zucco
Martine
M
Emeric
Gilbert
G
Delgado
Antonio
A
D000107:Acetylation; D000588:Amines / Q000737:chemistry; D000812:Anhydrides / Q000737:chemistry; D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016208:Databases, Factual; D004353:Drug Evaluation, Preclinical; D006017:Glycolipids / Q000737:chemistry; D015394:Molecular Structure; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects*; D013107:Sphingolipids / Q000096:biosynthesis / Q000737:chemistry; D019802:Succinic Acid / Q000737:chemistry* / Q000494:pharmacology*
D000588:Amines; D000812:Anhydrides; D000935:Antifungal Agents; D006017:Glycolipids; D013107:Sphingolipids; C109747:khafrefungin; D019802:Succinic Acid