title: Design and synthesis of a series of piperazine-1-carboxamidine derivatives with antifungal activity resulting from accumulation of endogenous reactive oxygen species.
abstract: In this study, we screened a library of 500 compounds for fungicidal activity via induction of endogenous reactive oxygen species (ROS) accumulation. Structure-activity relationship studies showed that piperazine-1-carboxamidine analogues with large atoms or large side chains substituted on the phenyl group at the R(3) and R(5) positions are characterized by a high ROS accumulation capacity in Candida albicans and a high fungicidal activity. Moreover, we could link the fungicidal mode of action of the piperazine-1-carboxamidine derivatives to the accumulation of endogenous ROS.
authors.affiliation: Centre of Microbial and Plant Genetics, Katholieke Universiteit Leuven, Kasteelpark Arenberg 20, 3001 Heverlee (Belgium).
authors.forename: Isabelle E
authors.initials: IE
authors.lastname: François
authors.forename: Karin
authors.initials: K
authors.lastname: Thevissen
authors.forename: Klaartje
authors.initials: K
authors.lastname: Pellens
authors.forename: Els M
authors.initials: EM
authors.lastname: Meert
authors.forename: Jan
authors.initials: J
authors.lastname: Heeres
authors.forename: Eddy
authors.initials: E
authors.lastname: Freyne
authors.forename: Erwin
authors.initials: E
authors.lastname: Coesemans
authors.forename: Marcel
authors.initials: M
authors.lastname: Viellevoye
authors.forename: Frederik
authors.initials: F
authors.lastname: Deroose
authors.forename: Sonia
authors.initials: S
authors.lastname: Martinez Gonzalez
authors.forename: Joaquin
authors.initials: J
authors.lastname: Pastor
authors.forename: David
authors.initials: D
authors.lastname: Corens
authors.forename: Lieven
authors.initials: L
authors.lastname: Meerpoel
authors.forename: Marcel
authors.initials: M
authors.lastname: Borgers
authors.forename: Jannie
authors.initials: J
authors.lastname: Ausma
authors.forename: Gerrit D
authors.initials: GD
authors.lastname: Dispersyn
authors.forename: Bruno P
authors.initials: BP
authors.lastname: Cammue
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000378:metabolism; D015195:Drug Design; D010879:Piperazines / Q000138:chemical synthesis / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D010879:Piperazines; D017382:Reactive Oxygen Species