Antifungal properties of novel N- and alpha,beta-substituted succinimides against dermatophytes.
The synthesis and antifungal properties of a series of new N-aryl alpha,beta-substituted succinimides against a panel of dermatophytes of clinical relevance are reported. Among those compounds possessing a N-phenyl substituent, 7-thia-2-azabicyclo[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-sulfonylphenyl) substituent, only inhibited Epidermophyton floccosum, all active compounds possessing an oxabicyclo group in positions alpha,beta of the imide. Substituents on the oxabicyclo group were important for the activity. Regarding the mechanism of action, N-(p-N'-4-methoxyphenylsulfamoylphenyl)-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.
López
Silvia N
SN
Facultad Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional Rosario, Rosario, Argentina.
Sortino
Maximiliano
M
Escalante
Andrea
A
de Campos
Fátima
F
Corrêa
Rogério
R
Cechinel Filho
V
V
Nunes
Ricardo J
RJ
Zacchino
Susana A
SA
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D003883:Arthrodermataceae / Q000187:drug effects* / Q000648:ultrastructure; D008826:Microbial Sensitivity Tests; D009492:Neurospora crassa / Q000187:drug effects / Q000648:ultrastructure; D013388:Succinimides / Q000138:chemical synthesis* / Q000494:pharmacology*
D000935:Antifungal Agents; D013388:Succinimides