New systematically active antimycotics from the beta-blocker category.
Candida albicans secretes phospholipases, which are considered to be one of the mediators of cell penetration. It is known that other phospholipases from mammalian cells can be inhibited by lipophilic beta-blocking structures. As the result of a synthesis programme of several years' duration, structures deriving from beta-hydroxyethylamines were introduced. In vitro and in vivo results with these compounds are presented in comparison with standard antimycotics. In combination with fluconazole, several of the compounds can prevent death in mice infected with lethal inocula of C. albicans. Histological examinations confirm the inhibitory effect of the beta-blocker-like structures on tissue penetration. The structures therefore constitute new antimycotics that are endowed with extensive in vitro effectiveness against fungi and also definite in vivo effects in the animal model.
Hänel
H
H
Hoechst AG, Frankfurt/Main, Germany.
Kirsch
R
R
Schmidts
H L
HL
Kottmann
H
H
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development / Q000472:pathogenicity; D002177:Candidiasis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005656:Fungal Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D010740:Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D000935:Antifungal Agents; D005656:Fungal Proteins; D010740:Phospholipases