Antifungal properties of novel N- and a,b substituted succinimides against dermatophytes

SILVIA LOPEZ; MAXIMILANO SORTINO; ANDREA ESCALANTE; FATIMA CAMPOS; ROGELIO CORREA; VALDIR CECHINEL FILHO; SUSANA ZACCHINO

ARZNEIMITTEL FORSCHUNG DRUG RESEARCH

Editio Cantor Verlag

Lugar: Herdecke, Alemania; Año: 2003 vol. 53 p. 280 - 288

0004-4172

The synthesis end antifungal properties of a series of new N-aryl a,b-substituted succinimides against a panel of dermatophytes of clinical relevance are reported. Among those compounds possesing a N-phenyl subtituent, 7-thia-2-aza-bicyclo[2,2,1]hept-2-en-3-amine[5,6-c]succinimide was the better inhibitor of Trichophyton rubrum, the major ethiological agent of all infections produced by dermatophytes. In contrast, succinimides containing a N-(p-sulfophenyl) substituent, only inhibited Epidermophyton floccosum, all active compounds possessing an  oxybicyclo group in possitions a,b of the imide. Substituents on the oxabicyclo group were important for the activity. Regarding the mechanism of action, N-(p-N´-4-methoxyphenylsulfamoyl-phenyl)-8-oxabicyclo[2,2,1] hept-4-en-3-methyl[5,6-c]succinimide produced a mottled inhibition halo in the Neurospora crassa assay, showing that it would act by inhibiting the synthesis or assembly of the fungal cell wall.