title: Molecular Docking Evaluation of Imidazole Analogues as Potent Candida albicans 14α-Demethylase Inhibitors.
abstract: Candida albicans is one of the most important causes of life-threating fungal infections. Lanosterol 14α-demethylase (Cytochrome P450DM) is the target enzyme of azole antifungal agents. The study involved selection and modeling of the target enzyme followed by refinement of the model using molecular dynamic simulation. The modeled structure of enzyme was validated using Ramachandran plot and Sequence determination technique. A series of chlorosubstituted imidazole analogues were evaluated for Cytochrome P450 inhibitory activity using molecular docking studies. The imidazole analogues were prepared using Chem sketch and molecular docking was performed using Molergo Virtual Docker program. The docking study indicated that all the imidazole analogues (AN1-AN45) and standard drugs i.e., Ketoconazole, Clotrimazole and Miconazole have interaction with protein residue of 14α-demethylase, Heme cofactor and the water molecules present in the active site.
authors.affiliation: Guru Gobind Singh College of Pharmacy, Yamuna Nagar, Haryana, India. nidhiprajapati8@gmail.com.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Rani
authors.forename: Praveen
authors.initials: P
authors.lastname: Kumar
authors.forename: Randhir
authors.initials: R
authors.lastname: Singh
authors.forename: Ajay
authors.initials: A
authors.lastname: Sharma
mesh_terms: D058888:14-alpha Demethylase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000201:enzymology*; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D058886:Sterol 14-Demethylase / Q000737:chemistry / Q000378:metabolism*
chemical_list: D058888:14-alpha Demethylase Inhibitors; D000935:Antifungal Agents; D007093:Imidazoles; C029899:imidazole; D058886:Sterol 14-Demethylase