In vitro antifungal properties, structure-activity relationships and studies on mode of action of N-phenyl, N-aryl, N-alkylphenyl maleimides and related compounds

S.N.LOPEZ, M.V.CASTELLI, F.ROGERIO CORREA, V.CECHINEL FILHO, R A.YUNES, M.A.ZAMORA, R.D.ENRIZ, J.C.RIBAS, S.A.ZACCHINO

ARZNEIMITTEL FORSCHUNG DRUG RESEARCH

Cantor Verlag

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

0004-4172

The synthesis, in vitro antifungal evalu- 59 ation and structure-activity relationshipation and structure-activity relationship 60 studies of 14 compounds of the N-studies of 14 compounds of the N- 61 phenyl-, N-aryl-, N-phenylalkyl- maleim-phenyl-, N-aryl-, N-phenylalkyl- maleim- 62 ide and 3,4-dichloromaleimide series areide and 3,4-dichloromaleimide series are 63 reported. The compounds were evaluatedreported. The compounds were evaluated 63 63 63 63 - Spalte 2 -- Spalte 2 - 63 64 against a panel of standardized yeastsagainst a panel of standardized yeasts 65 and filamentous fungi as well as clinicaland filamentous fungi as well as clinical 66 isolates of Candida albicans. The activ-isolates of Candida albicans. The activ- 67 ities of N-phenylalkyl-3,4-dichloromalei-ities of N-phenylalkyl-3,4-dichloromalei- 68 mide derivatives but not those of N-mide derivatives but not those of N- 69 phenylalkyl-maleimide derivativesphenylalkyl-maleimide derivatives 70 showed to be dependent on the length ofshowed to be dependent on the length of 71 the alkyl chain. N-Phenylpropyl-3,4-the alkyl chain. N-Phenylpropyl-3,4- 72 dichloromaleimide showed the broadestdichloromaleimide showed the broadest 73 spectrum of action and lower minimal in-spectrum of action and lower minimal in- 74 hibitory concentrations (MIC) in all ofhibitory concentrations (MIC) in all of 75 the fungi tested. The nitrogen-carbon dis-the fungi tested. The nitrogen-carbon dis- 76 tance between the two rings seems totance between the two rings seems to 77 play an important role in the antifungalplay an important role in the antifungal 78 behavior of these compounds. The mostbehavior of these compounds. The most 79 active structure showed inhibited (1,3)â-active structure showed inhibited (1,3)â-