Antifungal Spectrum, in vivo Efficacy and Structure Activity Relationship of Ilicicolin H

Ref ID: 18681

Author:

S. Singh, PhD (Doctor of Philosophy) – Program Lead, W. Liu, PhD – team member, X. Li, MS – Research Assistant, T. Chen, PhD – Sr. Investigator, A. Shafiee, PhD – Sr Research Fellow, D. Card, MS – Program Lead, G. Abruzzo, MS – Research Associate, A.

Author address:

Merck & Co., Inc., Rahway, NJ.

Full conference title:

52nd Annual ICAAC

Date: 9 September 2014

Abstract:

Background: This study aimed to characterize and develop ilicicolin H, a natural product, as an antifungal agent Methods: Whole cell antifungal MIC, NADH: cytochrome c1 oxidoreductase activity against yeast and rat liver, in vivo efficacy in murine model. Chemical modifications to the molecule were made by chemicals and biotransformation approaches. Results: Ilicicolin H exhibits potent and broad spectrum antifungal activity, with sub micro g/mL MICs against Candida spp, Aspergillus fumigatus and Cryptococcus spp. It showed a novel mode of action, potent inhibition (IC50 2-3 ng/mL) of the mitochondrial cytochrome bc1 reductase, and over 1000-fold selectivity relative to rat liver cytochrome bc1 reductase. Ilicicolin H exhibited in vivo efficacy in murine models of Candida albicans and Cryptococcus neoformans infections, but efficacy may have been limited by high plasma protein binding. Systematic structural modification of ilicicolin H was undertaken to understand the structural requirement for the antifungal activity. Conclusions: Ilicicolin H is showed broad-spectrum antifungal activities, inhibits cytochrome bc1 complex, and showed in vivo efficacy against murine model of Candida and Cryptococcus infection

Abstract Number: F-810

Conference Poster: y

Conference Year: 2012

Link to conference website: NULL

New link: NULL

Conference abstracts, posters & presentations

Showing 10 posts of 17325 posts found.

  • Title

    Author

    Year

    Number

    Poster