Differential inhibition of fungal amd mammalian squalene epoxidases by the benzylamine SDZ SBA 586 in comparison with the allylamine terbinafine

Détails

ID Serval
serval:BIB_F1C81D906C6F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Differential inhibition of fungal amd mammalian squalene epoxidases by the benzylamine SDZ SBA 586 in comparison with the allylamine terbinafine
Périodique
Archives of Biochemistry and Biophysics
Auteur(s)
Favre  B., Ryder  N. S.
ISSN
0003-9861 (Print)
Statut éditorial
Publié
Date de publication
04/1997
Volume
340
Numéro
2
Pages
265-9
Notes
Comparative Study
Journal Article --- Old month value: Apr 15
Résumé
The allylamine class of antifungal compounds are specific inhibitors of squalene epoxidase (SE). However, depending on their chemical structure, allylamine derivatives can be highly selective for either fungal or mammalian SEs. All allylamines tested previously, irrespective of their selectivity, inhibit fungal SEs in a noncompetitive manner and mammalian SEs in a competitive manner. Here we have analyzed the inhibitory properties of the benzylamine SDZ SBA 586 toward fungal and mammalian SEs in comparison to the systemic antimycotic terbinafine, SDZ SBA 586 was, like terbinafine a selective inhibitor of fungal SE. Microsomal SE from the pathogenic yeast candida albicans was sixfold more sensitive to SDZ SBA 586 than to terbinafine, C50: 8 nM versus 44 nM, while the enzyme from the dermatophyte fungus Trichophyton rubrum was slightly less sensitive to SDZ SBA 586 than to terbinafine, IC50: 39 and 18 nM, respectively. Similarly to terbinafine, SDZ SBA 586 inhibited the yeast enzyme in non competitive manner, SDZ SBA 586 also inhibited mammalian microsomal SEs, but only at micromolar concentrations. It was more active than terbinafine toward both guinea pig SE, IC50: 2 microM versus 4 microM, and rat SE, IC50: 11 microM versus 87 microM. However, in contrast to terbinafine as well as allylamines selective for mammalian SE, SDZ SBA 586 was a noncompetitive inhibitor of rat microsomal SE. Interestingly, depending on the source of microsomal SE, binding of terbinafine and SDZ SBA 586 exhibited a positive, indifferent, or negative cooperativity, suggesting that SE is an oligomeric enzyme.
Mots-clé
Allosteric Regulation Animals Antifungal Agents/*pharmacology Benzylamines/*pharmacology Binding Sites Candida albicans/enzymology Enzyme Inhibitors/*pharmacology Kinetics Microsomes/enzymology Naphthalenes/*pharmacology Oxygenases/*antagonists & inhibitors Rats Species Specificity Squalene Monooxygenase Trichophyton/*enzymology
Pubmed
Web of science
Création de la notice
25/01/2008 17:32
Dernière modification de la notice
03/03/2018 22:39
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