Abstract
Several N-substituted maleimides containing substituents of varying bulkiness and polarity were synthesised and tested for antimicrobial and cytostatic activity. Neutral maleimides displayed relatively strong antifungal effect minimum inhibitory concentrations (MICs in the 0.5-4 µg ml(-1) range); their antibacterial activity was structure dependent and all were highly cytostatic, with IC(50) values below 0.1 µg ml(-1). Low antimicrobial but high cytostatic activity was noted for basic maleimides containing tertiary aminoalkyl substituents. Chemical reactivity and lipophilicity influenced antibacterial activity of neutral maleimides but had little if any effect on their antifungal and cytostatic action. N-substituted maleimides affected biosynthesis of chitin and β(1,3)glucan, components of the fungal cell wall. The membrane enzyme, β(1,3)glucan synthase has been proposed as a putative primary target of N-ethylmaleimide and some of its analogues in Candida albicans cells.
MeSH terms
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Anti-Bacterial Agents / chemical synthesis
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / pharmacology*
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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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Bacillus subtilis / drug effects
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Candida albicans / cytology
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Candida albicans / drug effects*
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Cell Proliferation / drug effects
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Cytostatic Agents / chemical synthesis
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Cytostatic Agents / chemistry
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Cytostatic Agents / pharmacology*
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Escherichia coli / drug effects
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Glucosyltransferases / antagonists & inhibitors
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Glucosyltransferases / metabolism
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HeLa Cells
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Humans
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Maleimides / chemical synthesis
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Maleimides / chemistry
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Maleimides / pharmacology*
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Microbial Sensitivity Tests
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Molecular Structure
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Staphylococcus aureus / drug effects
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Structure-Activity Relationship
Substances
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Anti-Bacterial Agents
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Antifungal Agents
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Cytostatic Agents
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Enzyme Inhibitors
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Maleimides
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maleimide
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Glucosyltransferases
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1,3-beta-glucan synthase