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Design, synthesis and determination of antifungal activity of 5(6)-substituted benzotriazoles

Pallav D PD Patel, Maulik R MR Patel, Bela B Kocsis, Erika E Kocsis, Steven M SM Graham, Andrew R AR Warren, Stacia M SM Nicholson, Blase B Billack, Frank R FR Fronczek, and Tanaji T TT Talele

Eur J Med Chem 45(6):9 (2010) PMID 20181413

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@mg/mL to 25@mg/mL and 12.5@mg/mL to 25@mg/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.

Copyright © 2010 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.ejmech.2010.01.062
Version: za2963e q8za6 q8zb7 q8zc2 q8zd1 q8ze9 q8zf1 q8zg7

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