title: 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.
abstract: 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.
authors.affiliation: Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Silvia N
authors.initials: SN
authors.lastname: López
authors.forename: María V
authors.initials: MV
authors.lastname: Castelli
authors.forename: Fátima
authors.initials: F
authors.lastname: de Campos
authors.forename: Rogerio
authors.initials: R
authors.lastname: Corrêa
authors.forename: Valdir
authors.initials: V
authors.lastname: Cechinel Filho
authors.forename: Rosendo A
authors.initials: RA
authors.lastname: Yunes
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Zamora
authors.forename: Ricardo D
authors.initials: RD
authors.lastname: Enriz
authors.forename: Juan C
authors.initials: JC
authors.lastname: Ribas
authors.forename: Ricardo L E
authors.initials: RL
authors.lastname: Furlán
authors.forename: Susana A
authors.initials: SA
authors.lastname: Zacchino
mesh_terms: 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
chemical_list: D000935:Antifungal Agents; D008301:Maleimides; D005964:Glucosyltransferases; D002687:Chitin Synthase; C020570:1,3-beta-glucan synthase