Synthesis and fungicidal activity of 3,5-dichloropyrazin-2(1H)-one derivatives

Isabelle E J A François; Bruno P A Cammue; Sara Bresseleers; Hein Fleuren; Georges Hoornaert; Vaibhav P Mehta; Sachin G Modha; Erik V Van der Eycken; Karin Thevissen

doi:10.1016/j.bmcl.2009.06.024

Synthesis and fungicidal activity of 3,5-dichloropyrazin-2(1H)-one derivatives

Bioorg Med Chem Lett. 2009 Aug 1;19(15):4064-6. doi: 10.1016/j.bmcl.2009.06.024. Epub 2009 Jun 13.

Authors

Isabelle E J A François¹, Bruno P A Cammue, Sara Bresseleers, Hein Fleuren, Georges Hoornaert, Vaibhav P Mehta, Sachin G Modha, Erik V Van der Eycken, Karin Thevissen

Affiliation

¹ Centre of Microbial and Plant Genetics, Katholieke Universiteit Leuven, Kasteelpark Arenberg 20, B-3001 Heverlee, Belgium.

PMID: 19556127
DOI: 10.1016/j.bmcl.2009.06.024

Abstract

We synthesized a family of 3,5-dichloropyrazin-2(1H)-one derivatives and assessed their in vitro fungicidal activity against Candida albicans. Compounds 11 and 20 were most active against C. albicans and induced accumulation of reactive oxygen species in this pathogen. Using a genome-wide approach in the yeast Saccharomyces cerevisiae, we demonstrated that genes involved in vacuolar functionality and DNA-related functions play an important role in cellular mechanisms underlying the fungicidal activity of these compounds.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antifungal Agents / pharmacology*
Candida albicans / metabolism
DNA / chemistry
Drug Resistance, Fungal / drug effects
Fungal Proteins / genetics
Fungal Proteins / metabolism
Gene Deletion
Genome, Fungal
Microbial Sensitivity Tests
Models, Chemical
Mutation
Pyrazines / chemical synthesis
Pyrazines / chemistry*
Pyrazines / pharmacology*
Saccharomyces cerevisiae / metabolism
Vacuoles / chemistry

Substances

Antifungal Agents
Fungal Proteins
Pyrazines
DNA