Dual inhibition of the α-glucosidase and butyrylcholinesterase studied by molecular field topology analysis

  • Eur J Med Chem. 2014 Jun 10:80:228-42. doi: 10.1016/j.ejmech.2014.04.018.
Farukh Jabeen  1 ,  Polina V Oliferenko  2 ,  Alexander A Oliferenko  2 ,  Girinath G Pillai  3 ,  Farzana Latif Ansari  4 ,  C Dennis Hall  5 ,  Alan R Katritzky  6
Affiliations
  • 1. Department of Chemistry, University of Florida, PO Box 117200, Gainesville, FL 32611, USA; Department of Chemistry, Quaid i Azam University, Islamabad 45320, Pakistan.
  • 2. Department of Chemistry, University of Florida, PO Box 117200, Gainesville, FL 32611, USA.
  • 3. Department of Chemistry, University of Florida, PO Box 117200, Gainesville, FL 32611, USA; Department of Chemistry, University of Tartu, Tartu 50411, Estonia.
  • 4. Department of Chemistry, Quaid i Azam University, Islamabad 45320, Pakistan.
  • 5. Department of Chemistry, University of Florida, PO Box 117200, Gainesville, FL 32611, USA. Electronic address: [email protected].
  • 6. Department of Chemistry, University of Florida, PO Box 117200, Gainesville, FL 32611, USA. Electronic address: [email protected].
PMID: 24780600 DOI: 10.1016/j.ejmech.2014.04.018
Abstract

A striking dual inhibition of Enzymes α-glucosidase and butyrylcholinesterase by small drug-like molecules, including 1,4-disubstituted-1,2,3-triazoles, Chalcones, and benzothiazepines, was rationalized with the help of Molecular Field Topology Analysis, a 3D QSAR technique similar to CoMFA. A common pharmacophore supported the concept of a link existing between type-2 diabetes mellitus and Alzheimer's disease. These findings will be instrumental for rational design of drug candidates for both of these conditions.

Keywords
Butyrylcholinesterase; Inhibitors; MFTA; QSAR; α-Glucosidase.
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