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New azole antifungals with a fused triazinone scaffold.

Abstract：

:We identified a new series of azole antifungal agents bearing a pyrrolotriazinone scaffold. These compounds exhibited a broad in vitro antifungal activity against pathogenic Candida spp. (fluconazole-susceptible and fluconazole-resistant) and were 10- to 100-fold more active than voriconazole against two Candida albicans isolates with known mechanisms of azole resistance (overexpression of efflux pumps and/or specific point substitutions in the Erg11p/CYP51 enzyme). Our lead compound 12 also displayed promising in vitro antifungal activity against some filamentous fungi such as Aspergillus fumigatus and the zygomycetes Rhizopus oryzae and Mucor circinelloides and an in vivo efficiency against two murine models of lethal systemic infections caused by Candida albicans.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Montoir D,Guillon R,Gazzola S,Ourliac-Garnier I,Soklou KE,Tonnerre A,Picot C,Planchat A,Pagniez F,Le Pape P,Logé C

doi

10.1016/j.ejmech.2020.112082

subject

Has Abstract

pub_date

2020-03-01 00:00:00

pages

112082

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(20)30049-0

journal_volume

189

pub_type

杂志文章

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