Antifungal activity of synthetic di(hetero)arylamines based on the benzo[b]thiophene moiety.
The antifungal activity of several di(hetero)arylamine derivatives of the benzo[b]thiophene system was evaluated against clinically relevant Candida, Aspergillus, and dermatophyte species by a broth macrodilution test based on CLSI (formerly NCCLS) guidelines. The most active compound showed a broad spectrum of activity (against all tested fungal strains, including fluconazole-resistant fungi), with particularly low MICs for dermatophytes. Results from the inhibition of the dimorphic transition in Candida albicans and flow cytometry studies further confirmed their biological activity. With this study it was possible to establish some structure-activity relationships (SARs). The hydroxy groups proved to be essential for the activity in the aryl derivatives. Furthermore, the spectrum of activity in the pyridine derivatives was broadened by the absence of the ester group on position 2 of the benzo[b]thiophene system.
Pinto
Eugénia
E
Centro de Química Medicinal, Faculdade de Farmácia, Rua Aníbal Cunha, 164, 4050-047 Porto, Portugal. epinto@ff.up.pt
Queiroz
Maria-João R P
MJ
Vale-Silva
Luís A
LA
Oliveira
João F
JF
Begouin
Agathe
A
Begouin
Jeanne-Marie
JM
Kirsch
Gilbert
G
D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003883:Arthrodermataceae / Q000187:drug effects; D001230:Aspergillus / Q000187:drug effects; D002175:Candida / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry / Q000379:methods; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry*
D000588:Amines; D000935:Antifungal Agents; D013876:Thiophenes; C088015:benzothiophene