Antifungal activity and studies on mode of action of novel xanthoxyline-derived chalcones.
Chalcones and chalcone-like compounds, most of them new ones, prepared by base-catalyzed condensation of appropriate aldehydes and xanthoxyline, were tested for antifungal properties against a panel of yeasts, hialohyphomycetes as well as dermatophytes with the agar dilution assay. Results indicate that neither the sole presence of a "xanthoxyline-like" substitution pattern nor a 2'-OH substituent on ring A are sufficient for these compounds to have antifungal properties. The chalcone 3-(2-chlorophenyl)-1-(2'-hydroxy-4',6'-dimethoxyphenyl)prop-2-en-1-one, with a Cl atom in the ortho position of benzene ring B showed the best antifungal activity against standardized strains of Trichophyton rubrum (MIC = 12.5 microg/mL) and inhibited all of the ten clinical isolates of T. rubrum tested (MIC at which 50 % [MIC(50)] and 90 % [MIC(90)] of the isolates were inhibited = 12.5 and 25 microg/mL). Regarding its mode of action, the Neurospora crassa assay showed a blotchy appearance in the inhibition halo produced by this chalcone, strongly suggesting that it could act by inhibiting the fungal cell wall. This chalcone seems to be an hyphal malformation inducer, since a clear curling of the hypha was observed in this hazy zone at a magnification of x 400. This work strongly contributes to the knowledge of the antifungal properties of hydroxy-chalcones.
Boeck
Paula
P
Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, Brasil.
Leal
Paulo C
PC
Yunes
Rosendo A
RA
Filho
Valdir Cechinel
VC
López
Silvia
S
Sortino
Maximiliano
M
Escalante
Andrea
A
Furlán
Ricardo L E
RL
Zacchino
Susana
S
D000098:Acetophenones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003883:Arthrodermataceae / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
D000098:Acetophenones; D000935:Antifungal Agents; D047188:Chalcones; C064382:xanthoxyline