Imidazolylchromanones containing non-benzylic oxime ethers: Synthesis and molecular modeling study of new azole antifungals selective against Cryptococcus gattii

A series of imidazolylchromanone oximes containing phenoxyethyl ether moiety, as found in omoconazole, were synthesized and evaluated against yeasts (Candida albicans and Cryptococcus gattii) and filamentous fungi (Aspergillus fumigatus and Exophiala dermatitidis). Although the title compounds showed marginal activity against filamentous fungi but all of them exhibited potent activity against C gattii (MIC values <= 4 mu g/mL). Among them, (3-chlorophenoxy)ethyl analog 7c with MIC value of 0.5 mu g/mL was the most potent compound. Further molecular docking studies provided a better insight into the binding of designed compounds within the homology modeled active site of CnCYP51 (Cryptococcus CYP51-14 alpha-demethylase). (C) 2014 Elsevier Masson SAS. All rights reserved.