title: 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.
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.
authors.affiliation: EMC microcollections GmbH, Sindelfinger Strasse 3, 72070 Tübingen, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Bauer
authors.forename: Stephan
authors.initials: S
authors.lastname: Kinast
authors.forename: Anke
authors.initials: A
authors.lastname: Burger-Kentischer
authors.forename: Doris
authors.initials: D
authors.lastname: Finkelmeier
authors.forename: Gerald
authors.initials: G
authors.lastname: Kleymann
authors.forename: Walid Abu
authors.initials: WA
authors.lastname: Rayyan
authors.forename: Klaus
authors.initials: K
authors.lastname: Schröppel
authors.forename: Anurag
authors.initials: A
authors.lastname: Singh
authors.forename: Günther
authors.initials: G
authors.lastname: Jung
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Wiesmüller
authors.forename: Steffen
authors.initials: S
authors.lastname: Rupp
authors.forename: Holger
authors.initials: H
authors.lastname: Eickhoff
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D050256:Antimitotic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D002175:Candida / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D057166:High-Throughput Screening Assays; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D008826:Microbial Sensitivity Tests; D009172:Mycology / Q000379:methods; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: C568522:2-(1-aminoisobutyl)-1-(3-chlorobenzyl)benzimidazole; D000935:Antifungal Agents; D050256:Antimitotic Agents; D001562:Benzimidazoles; D007093:Imidazoles