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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antifungal Agents / chemical synthesis
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Antifungal Agents / pharmacology
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Antifungal Agents / toxicity
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Antimitotic Agents / chemical synthesis*
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Antimitotic Agents / pharmacology
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Antimitotic Agents / toxicity
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Benzimidazoles / chemical synthesis*
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Benzimidazoles / pharmacology
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Benzimidazoles / toxicity
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Candida / drug effects
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Candida / genetics
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Cell Line, Tumor
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Drug Screening Assays, Antitumor
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High-Throughput Screening Assays
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Humans
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Imidazoles / chemical synthesis
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Imidazoles / pharmacology
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Imidazoles / toxicity
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Microbial Sensitivity Tests
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Mycology / methods
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Stereoisomerism
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Structure-Activity Relationship
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Transcription, Genetic / drug effects
Substances
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2-(1-aminoisobutyl)-1-(3-chlorobenzyl)benzimidazole
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Antifungal Agents
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Antimitotic Agents
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Benzimidazoles
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Imidazoles