Abstract
Semisynthetic modifications at Hydroxy tyrosine (Htyr) unit of mulundocandin (1) were carried out to improve its aqueous solubility. A single step introduction of substituted aminomethyl groups at the ortho position(s) of phenolic hydroxyl of HTyr unit of mulundocandin has been achieved in 7-85% yield. The in vitro screening of Mannich products against Candida albicans and Aspergillus fumigatus, retained the in vivo activity of parent by oral and intraperitoneal route. Compound 20, showed significant improvement in activity over mulundocandin (1) and activity compares well with that of fluconazole.
MeSH terms
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Animals
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Antifungal Agents / administration & dosage
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Antifungal Agents / chemistry*
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Antifungal Agents / pharmacology
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Candida albicans / drug effects
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Candidiasis / drug therapy
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Disease Models, Animal
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Drug Evaluation, Preclinical
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Echinocandins
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Mannich Bases / administration & dosage
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Mannich Bases / chemical synthesis*
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Mannich Bases / pharmacology
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Mice
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Microbial Sensitivity Tests
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Models, Animal
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Molecular Structure
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Peptides, Cyclic / administration & dosage
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Peptides, Cyclic / chemistry*
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Peptides, Cyclic / pharmacology
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Solubility
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Water / chemistry*
Substances
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Antifungal Agents
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Echinocandins
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Mannich Bases
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Peptides, Cyclic
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Water
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mulundocandin