title: Design and synthesis of new fluconazole analogues.
abstract: We have synthesized new fluconazole analogues containing two different 1,2,3-triazole units in the side chain. The synthesis of new amide analogues using a variety of acids is also described. All the compounds showed very good antifungal activity. A hemolysis study of the most active compounds 6e and 13j showed that both compounds did not cause any hemolysis at the dilutions tested. These compounds did not exhibit any toxicity to L929 cells at MIC and lower concentrations. In the docking study, the overall binding mode of 6e and 13j appeared to be reasonable and provided a good insight into the structural basis of inhibition of Candida albicans Cyp51 by these compounds.
authors.affiliation: Organic Chemistry Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pashan, Pune 411 008, India. vs.pore@ncl.res.in.
authors.forename: Vandana S
authors.initials: VS
authors.lastname: Pore
authors.forename: Sandip G
authors.initials: SG
authors.lastname: Agalave
authors.forename: Pratiksha
authors.initials: P
authors.lastname: Singh
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Shukla
authors.forename: Vikash
authors.initials: V
authors.lastname: Kumar
authors.forename: Mohammad I
authors.initials: MI
authors.lastname: Siddiqi
mesh_terms: D058888:14-alpha Demethylase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology; D002460:Cell Line / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004912:Erythrocytes / Q000187:drug effects; D015725:Fluconazole / Q000031:analogs & derivatives*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D011817:Rabbits; D013329:Structure-Activity Relationship; D018675:Toxicity Tests
chemical_list: D058888:14-alpha Demethylase Inhibitors; D000935:Antifungal Agents; D015725:Fluconazole; D003577:Cytochrome P-450 Enzyme System