title: Imidazole clubbed 1,3,4-oxadiazole derivatives as potential antifungal agents.
abstract: A series of compounds in which 2-(4-ethyl-2-pyridyl)-1H-imidazole was clubbed with substituted 1,3,4-oxadiazole was synthesized and subjected to antifungal activity evaluation. In vitro assays indicated that several clubbed derivatives had excellent antifungal activity against different strains of laboratory and clinically isolated Candida species. Structural Activity Relationship (SAR) studies revealed that the presence and position of substituents on the phenyl ring of the 1,3,4-oxadiazole unit, guides the antifungal potential of the compounds, where compound 4b, 4c and 4g were found to be active against all the tested fungal strains. Impairment of ergosterol biosynthesis upon the concomitant treatment of 4b, 4c and 4g, revealed the possible mechanisms of antifungal action of these compounds. Inhibitors snugly fitting the active site of the target enzyme, as revealed by molecular docking studies, may well explain their excellent inhibitory activity.
authors.affiliation: Departmento de Quimica, FCTUC, Universidade de Coimbra, Rua Larga, Coimbra 3004-535, Portugal. Electronic address: waniyouns@gmail.com.
authors.forename: Mohmmad Younus
authors.initials: MY
authors.lastname: Wani
authors.affiliation: Department of Oral Biological Sciences, University of Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa.
authors.forename: Aijaz
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: Department of Chemistry, Faculty of Science, Taibah University, PO Box 30002, Al Madinah Al Munawarrah, Saudi Arabia.
authors.forename: Rayees Ahmad
authors.initials: RA
authors.lastname: Shiekh
authors.affiliation: Department of Chemistry, Faculty of Science, Taibah University, PO Box 30002, Al Madinah Al Munawarrah, Saudi Arabia.
authors.forename: Khalaf J
authors.initials: KJ
authors.lastname: Al-Ghamdi
authors.affiliation: Departmento de Quimica, FCTUC, Universidade de Coimbra, Rua Larga, Coimbra 3004-535, Portugal. Electronic address: asobral@ci.uc.pt.
authors.forename: Abilio J F N
authors.initials: AJFN
authors.lastname: Sobral
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007093:Imidazoles / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010069:Oxadiazoles / Q000737:chemistry*; D013261:Sterols / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D007093:Imidazoles; D010069:Oxadiazoles; D013261:Sterols; C583463:1,3,4-oxadiazole; C029899:imidazole
keywords: 1,3,4-Oxadiazole; Antifungal activity; Docking; Imidazole; Pyridine