Abstract
Based on the HTS hit compound 1a, an inhibitor of beta-1,6-glucan synthesis, we synthesized novel pyridobenzimidazole derivatives and evaluated their antifungal activity. Among the compounds synthesized, we identified the potent compound 15e, which exhibits excellent activity superior to fluconazole against both Candida glabrata and Candida krusei. From the SAR study, we revealed essential moieties for antifungal activity.
2010 Elsevier Ltd. All rights reserved.
MeSH terms
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Antifungal Agents / chemical synthesis
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Antifungal Agents / chemistry
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Antifungal Agents / pharmacology*
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Aspergillus fumigatus / drug effects*
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Benzimidazoles / chemical synthesis
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Benzimidazoles / chemistry
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Benzimidazoles / pharmacology*
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Candida / cytology
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Candida / drug effects*
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Candida / metabolism
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Cell Wall / drug effects
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Cell Wall / metabolism
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Dose-Response Relationship, Drug
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High-Throughput Screening Assays
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Microbial Sensitivity Tests
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Molecular Structure
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Stereoisomerism
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Structure-Activity Relationship
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beta-Glucans / antagonists & inhibitors*
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beta-Glucans / metabolism
Substances
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Antifungal Agents
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Benzimidazoles
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beta-Glucans
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beta-1,6-glucan