Three-dimensional QSAR analysis and design of new 1,2,4-oxadiazole antibacterials.

Autor: Leemans E; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA., Mahasenan KV; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA., Kumarasiri M; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA., Spink E; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA., Ding D; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA., O'Daniel PI; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA., Boudreau MA; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA., Lastochkin E; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA., Testero SA; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA., Yamaguchi T; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA., Lee M; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA., Hesek D; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA., Fisher JF; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA., Chang M; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA., Mobashery S; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA. Electronic address: mobashery@nd.edu.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2016 Feb 01; Vol. 26 (3), pp. 1011-1015. Date of Electronic Publication: 2015 Dec 12.
DOI: 10.1016/j.bmcl.2015.12.041
Abstrakt: The oxadiazole antibacterials, a class of newly discovered compounds that are active against Gram-positive bacteria, target bacterial cell-wall biosynthesis by inhibition of a family of essential enzymes, the penicillin-binding proteins. Ligand-based 3D-QSAR analyses by comparative molecular field analysis (CoMFA), comparative molecular shape indices analysis (CoMSIA) and Field-Based 3D-QSAR evaluated a series of 102 members of this class. This series included inactive compounds as well as compounds that were moderately to strongly antibacterial against Staphylococcus aureus. Multiple models were constructed using different types of energy minimization and charge calculations. CoMFA derived contour maps successfully defined favored and disfavored regions of the molecules in terms of steric and electrostatic properties for substitution.
(Copyright © 2016. Published by Elsevier Ltd.)
Databáze: MEDLINE
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