title: Design, synthesis and determination of antifungal activity of 5(6)-substituted benzotriazoles.
abstract: In an effort to find inhibitors that are effective against both Candida and Aspergillus spp., a series of 5(6)-(un)substituted benzotriazole analogs, represented by compounds 3a-3h and 3b'-3f', were prepared using a crystalline oxirane intermediate 1 previously synthesized in our laboratory. All the compounds were evaluated for inhibitory activity against various species of Candida and Aspergillus. Compounds 3b' (5,6-dimethylbenzotriazol-2-yl derivative), 3d (5-chlorobenzotriazol-1-yl derivative) and 3e' (6-methylbenzotriazol-1-yl derivative) exhibited potent antifungal activity, with the MICs for Candida spp. and Aspergillus niger, ranging from 1.6 microg/mL to 25 microg/mL and 12.5 microg/mL to 25 microg/mL, respectively. The present work describes the design, synthesis, regioisomer characterization (through COSY and NOESY 2D-NMR spectroscopy and single molecule X-ray crystallography), antifungal evaluation, molecular docking, and structure-activity relationships of the various 5(6)-(un)substituted benzotriazole analogs.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University, Jamaica, NY 11439, USA.
authors.forename: Pallav D
authors.initials: PD
authors.lastname: Patel
authors.forename: Maulik R
authors.initials: MR
authors.lastname: Patel
authors.forename: Bela
authors.initials: B
authors.lastname: Kocsis
authors.forename: Erika
authors.initials: E
authors.lastname: Kocsis
authors.forename: Steven M
authors.initials: SM
authors.lastname: Graham
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Warren
authors.forename: Stacia M
authors.initials: SM
authors.lastname: Nicholson
authors.forename: Blase
authors.initials: B
authors.lastname: Billack
authors.forename: Frank R
authors.initials: FR
authors.lastname: Fronczek
authors.forename: Tanaji T
authors.initials: TT
authors.lastname: Talele
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D005658:Fungi / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D001426:Bacterial Proteins; D014230:Triazoles; C012771:benzotriazole; D003577:Cytochrome P-450 Enzyme System; C501935:cytochrome P-450 CYP51, Mycobacterium tuberculosis