In vitro antifungal activity of some Mannich bases of conjugated styryl ketones.
Four Mannich bases of some conjugated styryl ketones IIa-IId were examined for antifungal activity. These compounds were designed as thiol-alkylators and had two centers for attack by cellular thiols. The most potent compounds IIa and IIb possessed hydrophobic, electron-attracting substituents in the aryl rings and in general had minimum inhibitory concentration (MIC) values of 0.2-25 microM against a variety of fungi. None of the four compounds inhibited the growth of a number of bacteria (MIC > 100 microM). The minimum fungicidal concentration (MFC) values for IIa and IIb were generally either similar or twofold higher than the MIC figures for fungi. Compound IIa demonstrated rapid, concentration-dependent inhibition of the growth of Candida albicans B311. The toxicity of IIa to normal human cells was much lower than the concentrations of this compound required to inhibit fungal growth. In summary, this study of four prototypic molecules has revealed that this class of compounds may have potential for further development as candidate antifungal agents.
Manavathu
E K
EK
Department of Medicine, Wayne State University, Detroit, MI 48201, USA. emanavat@med.wayne.edu
Vashishtha
S C
SC
Alangaden
G J
GJ
Dimmock
J R
JR
D000935:Antifungal Agents / Q000494:pharmacology*; D001230:Aspergillus / Q000187:drug effects; D007659:Ketones / Q000494:pharmacology*; D008352:Mannich Bases / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D004718:Saccharomycetales / Q000187:drug effects; D013343:Styrenes / Q000494:pharmacology*
D000935:Antifungal Agents; D007659:Ketones; D008352:Mannich Bases; D013343:Styrenes