In vitro Antifungal Properties, Structure-activity Relationships and Studies on Mode of Action of N-Phenyl, N-Aryl, N-Phenylalkyl Maleimides and Related Compounds

LOPEZ, SN; CASTELLI, MV; DE CAMPOS, F; CORREA, R; CECHIINEL FILHO, V; YUNES, RA; ZAMORA, MA; ENRIZ, RD; RIBAS, JC; FURLAN, RLE; ZACCHINO, SA

ARZNEIMITTEL FORSCHUNG DRUG RESEARCH

ECV · Editio Cantor Verlag

Lugar: Aulendorf; Año: 2005 vol. 55 p. 123 - 132

0004-4172

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 inhibited (1,3)- D-glucan and chitin synthases, enzymes that catalyze the synthesis of the major fungal cell-wall polymers.