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

Farukh Jabeen; Polina V Oliferenko; Alexander A Oliferenko; Girinath G Pillai; Farzana Latif Ansari; C Dennis Hall; Alan R Katritzky

doi:10.1016/j.ejmech.2014.04.018

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. Epub 2014 Apr 5.

Authors

Farukh Jabeen¹, Polina V Oliferenko², Alexander A Oliferenko², Girinath G Pillai³, Farzana Latif Ansari⁴, C Dennis Hall⁵, Alan R Katritzky⁶

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: charlesdennishall@gmail.com.
⁶ Department of Chemistry, University of Florida, PO Box 117200, Gainesville, FL 32611, USA. Electronic address: Katritzky@chem.ufl.edu.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Butyrylcholinesterase / metabolism*
Cholinesterase Inhibitors / chemistry*
Cholinesterase Inhibitors / pharmacology*
Drug Design*
Glycoside Hydrolase Inhibitors / chemistry*
Glycoside Hydrolase Inhibitors / pharmacology*
Inhibitory Concentration 50
Quantitative Structure-Activity Relationship
alpha-Glucosidases / metabolism*

Substances

Cholinesterase Inhibitors
Glycoside Hydrolase Inhibitors
Butyrylcholinesterase
alpha-Glucosidases