Chitin synthetase inhibitors

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Chapter: Medicinal Chemistry : Antifungal Agents

Chitin synthetase inhibitors : Nikomycin - Synthesis and Drug Profile

Antifungal Agents - Synthesis and Drug Profile

Chitin synthetase inhibitors


1. Nikomycin

Mode of action: Nikomycin competitively inhibits the chitin synthase, mimicking its substrate uridine diphosphate-N-acetyl glucosamine of fungi with C. albicans as the primary target organism. The enzyme is an integral membrane protein. Nikomycin Z has shown to act synergistically in vitro with fluconazole, ketoconzole, and tioconazole against C. albicans at minimum inhibitory concentration (MIC) levels of azoles.

Properties and uses: Nikomycin is a nucleoside peptide antibiotic that is produced by soil strains of Steptomyces tendae. It is found to be more potent than most azoles in inhibiting highly chitinous, dimorphic fungal pathogens, such as Coccidiodes imitis and Blastomyces dermatidis.

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