title: Synthesis and antifungal activity of 1,2,3-triazole containing fluconazole analogues.
abstract: Fluconazole based novel mimics containing 1,2,3-triazole were designed and synthesized as antifungal agents. Their antifungal activities were evaluated in vitro by measuring the minimal inhibitory concentrations (MICs). Compounds 12, 15, and 16 were found to be more potent against Candida fungal pathogens than control drugs fluconazole and amphotericin B. The studies presented here provide structural modification of fluconazole to give 1,2,3-trazole containing molecules. Furthermore, these molecules were evaluated in vivo against Candida albicans intravenous challenge in Swiss mice and antiproliferative activities were tested against human hepatocellular carcinoma Hep3B and human epithelial carcinoma A431. It was found that compound 12 resulted in 97.4% reduction in fungal load in mice and did not show any profound proliferative effect at lower dose (0.001 mg/ml).
authors.affiliation: Organic Chemistry Division, National Chemical Laboratory, Pune 411 008, India.
authors.forename: Nilkanth G
authors.initials: NG
authors.lastname: Aher
authors.forename: Vandana S
authors.initials: VS
authors.lastname: Pore
authors.forename: Nripendra N
authors.initials: NN
authors.lastname: Mishra
authors.forename: Awanit
authors.initials: A
authors.lastname: Kumar
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Shukla
authors.forename: Aanchal
authors.initials: A
authors.lastname: Sharma
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Bhat
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001647:Bile Acids and Salts / Q000378:metabolism; D002176:Candida albicans; D002177:Candidiasis / Q000188:drug therapy; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D015725:Fluconazole / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008956:Models, Chemical; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D001647:Bile Acids and Salts; D014230:Triazoles; D015725:Fluconazole