Design and synthesis of a series of piperazine-1-carboxamidine derivatives with antifungal activity resulting from accumulation of endogenous reactive oxygen species.
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.
François
Isabelle E
IE
Centre of Microbial and Plant Genetics, Katholieke Universiteit Leuven, Kasteelpark Arenberg 20, 3001 Heverlee (Belgium).
Thevissen
Karin
K
Pellens
Klaartje
K
Meert
Els M
EM
Heeres
Jan
J
Freyne
Eddy
E
Coesemans
Erwin
E
Viellevoye
Marcel
M
Deroose
Frederik
F
Martinez Gonzalez
Sonia
S
Pastor
Joaquin
J
Corens
David
D
Meerpoel
Lieven
L
Borgers
Marcel
M
Ausma
Jannie
J
Dispersyn
Gerrit D
GD
Cammue
Bruno P
BP
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
D000935:Antifungal Agents; D010879:Piperazines; D017382:Reactive Oxygen Species