Design, Synthesis, and in vitro Antifungal Activity of 1‐[(4‐Substituted‐benzyl)methylamino]‐2‐(2,4‐difluorophenyl)‐3‐(1H‐1,2,4‐triazol‐1‐yl)propan‐2‐ols
Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
Medientyp:
E-Artikel
Titel:
Design, Synthesis, and in vitro Antifungal Activity of 1‐[(4‐Substituted‐benzyl)methylamino]‐2‐(2,4‐difluorophenyl)‐3‐(1H‐1,2,4‐triazol‐1‐yl)propan‐2‐ols
Beschreibung:
<jats:title>Abstract</jats:title><jats:p>As part of our studies focused on the design of 1‐[((hetero)aryl‐ and piperidinylmethyl)amino]‐2‐phenyl‐3‐(1<jats:italic>H</jats:italic>‐1,2,4‐triazol‐1‐yl)propan‐2‐ols as antifungal agents, we report the development of new extended benzylamine derivatives substituted at the <jats:italic>para</jats:italic> position by sulfonamide or retrosulfonamide groups linked to alkyl or aryl chains. These molecules have broad‐spectrum antifungal activities not only against <jats:italic>Candida</jats:italic> spp., including fluconazole‐resistant strains, but also against a filamentous species (<jats:italic>A. fumigatus</jats:italic>). Concerning fluconazole resistance, selected compounds exhibit the capacity to overcome <jats:italic>CDR</jats:italic> and <jats:italic>ERG11</jats:italic> gene upregulation and to maintain antifungal activity despite a recognized critical CYP51 substitution in <jats:italic>C. albicans</jats:italic> isolates. Synthesis, investigation of the mechanism of action by sterol analysis in a <jats:italic>C. albicans</jats:italic> strain, and structure–activity relationships (SARs) are reported.</jats:p>