In vitro antifungal properties structure-activity relationships and studies on the mode of action of N-phenyl, N-aryl, N-phenylalkyl maleimides and related compounds.
The synthesis, in vitro antifungal evaluation and structure-activity relationship studies of 14 compounds of the N-phenyl-, N-aryl-, N-phenylalkyl- maleimide and 3,4-dichloromaleimide series are reported. The compounds were evaluated against a panel of standardized yeasts and filamentous fungi as well as clinical isolates of Candida albicans. The activities of N-phenylalkyl-3,4-dichloromaleimide derivatives but not those of N-phenylalkyl-maleimide derivatives showed to be dependent on the length of the alkyl chain. N-Phenylpropyl-3,4-dichloromaleimide showed the broadest spectrum of action and lower minimal inhibitory concentrations (MIC) in all of the fungi tested. The nitrogen-carbon distance between the two rings seems to play an important role in the antifungal behavior of these compounds. The most active structure showed inhibited (1,3)beta-D-glucan and chitin synthases, enzymes that catalyze the synthesis of the major fungal cell-wall polymers.
López
Silvia N
SN
Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina.
Castelli
María V
MV
de Campos
Fátima
F
Corrêa
Rogerio
R
Cechinel Filho
Valdir
V
Yunes
Rosendo A
RA
Zamora
Miguel A
MA
Enriz
Ricardo D
RD
Ribas
Juan C
JC
Furlán
Ricardo L E
RL
Zacchino
Susana A
SA
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002687:Chitin Synthase / Q000037:antagonists & inhibitors; D005658:Fungi / Q000187:drug effects; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors; D008301:Maleimides / Q000138:chemical synthesis* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D008301:Maleimides; D005964:Glucosyltransferases; D002687:Chitin Synthase; C020570:1,3-beta-glucan synthase