title: Imidazolylchromanones containing non-benzylic oxime ethers: synthesis and molecular modeling study of new azole antifungals selective against Cryptococcus gattii.
abstract: 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 μg/mL). Among them, (3-chlorophenoxy)ethyl analog 7c with MIC value of 0.5 μg/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 CYP51-14α-demethylase).
authors.affiliation: Student Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Babazadeh-Qazijahani
authors.affiliation: Department of Medical Mycology & Parasitology/Invasive Fungi Research Center (IFRC), Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Badali
authors.affiliation: Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Irannejad
authors.affiliation: Department of Medical Mycology & Parasitology/Invasive Fungi Research Center (IFRC), Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Mohammad Hosein
authors.initials: MH
authors.lastname: Afsarian
authors.affiliation: Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address: sd_emami@yahoo.com.
authors.forename: Saeed
authors.initials: S
authors.lastname: Emami
mesh_terms: D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001393:Azoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002839:Chromans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D056285:Cryptococcus gattii / Q000187:drug effects* / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D058886:Sterol 14-Demethylase / Q000737:chemistry / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D002839:Chromans; D058886:Sterol 14-Demethylase
keywords: Antifungal activity; Azole antifungals; Chroman-4-one; Cryptococcus; Imidazole; Lanosterol 14α-demethylase