title: Imidazolylchromanones containing alkyl side chain as lanosterol 14α-demethylase inhibitors: synthesis, antifungal activity and docking study.
abstract: Previously, 2-alkylchromans have been introduced as non-azole inhibitors of 14α-demethylase. Accordingly, we incorporated imidazole ring on the 3-position of 2-alkylchromanones to design new inhibitors of 14α-demethylase and potential antifungal agents. Thus, a series of 2-alkyl-3-imidazolylchromanones were synthesized starting from 2-hydroxyphenacyl bromide. The trans-configuration of compounds was confirmed by NMR-spectroscopy. The antifungal activity of title compounds were evaluated against different fungi in comparison with fluconazole and miconazole. trans-2-(1-Pentyl)-3-imidazolylchroman-4-one (4d) showed the most potent activity against yeasts comparable to fluconazole. The experimental data based on (1)H NMR spectroscopy revealed that 2-alkyl side chain and 3-imidazolyl moiety in compound 4d exist predominantly in the di-equatorial conformation. While docking study with 14α-demethylase demonstrated that the di-axial form of compound 4d can be considered as active conformation.
authors.affiliation: Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences , Sari , Iran .
authors.forename: Saeed
authors.initials: S
authors.lastname: Emami
authors.forename: Touba
authors.initials: T
authors.lastname: Banipoulad
authors.forename: Hamid
authors.initials: H
authors.lastname: Irannejad
authors.forename: Alireza
authors.initials: A
authors.lastname: Foroumadi
authors.forename: Mehraban
authors.initials: M
authors.lastname: Falahati
authors.forename: Mahtab
authors.initials: M
authors.lastname: Ashrafi-Khozani
authors.forename: Somaye
authors.initials: S
authors.lastname: Sharifynia
mesh_terms: D058888:14-alpha Demethylase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002867:Chromones / Q000138:chemical synthesis* / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D058888:14-alpha Demethylase Inhibitors; D000935:Antifungal Agents; D002867:Chromones