title: Synthesis and antifungal activity of 1-[(2-benzyloxy)phenyl]-2-(azol-1-yl)ethanone derivatives: exploring the scaffold flexibility.
abstract: Based on the N-(phenethyl)azole backbone of azole antifungals, we designed 1-[(2-benzyloxy)phenyl]-2-(azol-1-yl)ethanone derivatives 2 and 3, containing benzyloxyphenyl scaffold of croconazole. Also these compounds can be considered as flexible analogs, resulted from C2-C3 disconnection of 3'-chloro-3-imidazolylflavanone 1, recently described as antifungal agent. Thus, in this report, we describe the synthesis of 1-[(2-benzyloxy)phenyl]-2-(azol-1-yl)ethanone derivatives 2 and 3 and their biological evaluation against different pathogenic fungi. By comparing the antifungal activity profile of flexible compounds 2 and 3 with that of rigid analog 1, it can be inferred that lower susceptibilities (higher minimum inhibitory concentrations) were observed with flexible compounds. However, among the synthesized compounds, 1-[2-(2,4-dichlorobenzyloxy)phenyl]-2-(1H-imidazol-1-yl)ethanone hydrochloride (2g) showed comparable or more potent antifungal activity in comparison with fluconazole as a standard drug.
authors.affiliation: Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. sd_emami@yahoo.com
authors.forename: Saeed
authors.initials: S
authors.lastname: Emami
authors.forename: Motahare
authors.initials: M
authors.lastname: Kazemi-Najafabadi
authors.forename: Soughra
authors.initials: S
authors.lastname: Pashangzadeh
authors.forename: Alireza
authors.initials: A
authors.lastname: Foroumadi
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Faramarzi
authors.forename: Nasrin
authors.initials: N
authors.lastname: Samadi
authors.forename: Mehraban
authors.initials: M
authors.lastname: Falahati
authors.forename: Roohollah
authors.initials: R
authors.lastname: Fateh
authors.forename: Mahtab
authors.initials: M
authors.lastname: Ashrafi-Khozani
mesh_terms: D000098:Acetophenones / Q000138:chemical synthesis* / Q000737:chemistry; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001393:Azoles / Q000138:chemical synthesis / Q000737:chemistry; D005658:Fungi / Q000187:drug effects*; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: C573649:1-(2-(2,4-dichlorobenzyloxy)phenyl)-2-(1H-imidazol-1-yl)ethanone; D000098:Acetophenones; D000935:Antifungal Agents; D001393:Azoles; D007093:Imidazoles; C038699:acetophenone