Antifungal activity of bis-azasqualenes, inhibitors of oxidosqualene cyclase.
The antifungal activity and in vitro toxicity toward animal cells of two inhibitors of oxidosqualene cyclase, squalene bis-diethylamine (SBD) and squalene bis-diethylmethylammonium iodide (SBDI) were studied. Minimum inhibitory concentration (MIC) against dermatophytes and other fungi involved in cutaneous and systemic infections (12 isolates from seven species) were determined by the broth microdilution method based on the reference documents M38-A and M27-A2 of Clinical and Laboratory Standards Institute (CLSI). Both compounds exerted fungistatic activities, although with different action. SBDI was the more active compound and displayed low MIC values (in the 3.12-12.5 μg ml(-1) range) against Microsporum canis, Trichophyton mentagrophytes and one isolate of Scopulariopsis brevicaulis, while SBD showed MIC values against these species in the 3.12-25 μg ml(-1) range. Toxicity was tested on Madin-Darby canine kidney (MDCK) epithelial cells and human microvascular endothelial cells (HMEC). SBDI proved the less toxic compound: it inhibited M. canis, T. mentagrophytes and S. brevicaulis at concentrations below those found toxic for MDCK cells. HMEC were the more sensitive cells.
Voyron
Samuele
S
Dipartimento di Biologia Vegetale, Università degli Studi di Torino, Torino, Italy.
Rocco
Flavio
F
Ceruti
Maurizio
M
Forni
Paolo
P
Pla
Alessandra Fiorio
AF
Sarpietro
Maria Grazia
MG
Varese
Giovanna Cristina
GC
Marchisio
Valeria Filipello
VF
D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004285:Dogs; D005658:Fungi / Q000187:drug effects*; D006801:Humans; D019751:Intramolecular Transferases / Q000037:antagonists & inhibitors*; D008826:Microbial Sensitivity Tests; D013185:Squalene / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000633:toxicity
D000935:Antifungal Agents; D013185:Squalene; D019751:Intramolecular Transferases; C021924:lanosterol synthase