High-throughput-screening-based identification and structure-activity relationship characterization defined (S)-2-(1-aminoisobutyl)-1-(3-chlorobenzyl)benzimidazole as a highly antimycotic agent nontoxic to cell lines

  • J Med Chem. 2011 Oct 13;54(19):6993-7. doi: 10.1021/jm200571e.
Jörg Bauer  1 ,  Stephan Kinast ,  Anke Burger-Kentischer ,  Doris Finkelmeier ,  Gerald Kleymann ,  Walid Abu Rayyan ,  Klaus Schröppel ,  Anurag Singh ,  Günther Jung ,  Karl-Heinz Wiesmüller ,  Steffen Rupp ,  Holger Eickhoff
Affiliations
  • 1. EMC microcollections GmbH, Sindelfinger Strasse 3, 72070 Tübingen, Germany.
PMID: 21711055 DOI: 10.1021/jm200571e
Abstract

Novel nontoxic (S)-2-aminoalkylbenzimidazole derivatives were found to be effective against Candida spp. at low micromolar concentrations using high-throughput screening with infected HeLa cells. A collection of analogues defined the chemical groups relevant for activity. The most active compound was characterized by transcriptional analysis of the response of C. albicans Sc5314. (S)-2-(1-Aminoisobutyl)-1-(3-chlorobenzyl)benzimidazole had a strong impact on membrane biosynthesis. Testing different clinically relevant pathogenic fungi showed the selectivity of the antimycotic activity against Candida species.