Dual inhibition of the α-glucosidase and butyrylcholinesterase studied by Molecular Field Topology Analysis

• Published in: European journal of medicinal chemistry Vol. 80; pp. 228 - 242
• Main Authors: Jabeen, Farukh, Oliferenko, Polina V., Oliferenko, Alexander A., Pillai, Girinath G., Ansari, Farzana Latif, Hall, C. Dennis, Katritzky, Alan R.
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 10-06-2014
• Subjects: alpha-Glucosidases - metabolism; Butyrylcholinesterase; Butyrylcholinesterase - metabolism; Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - pharmacology; Drug Design; Glycoside Hydrolase Inhibitors - chemistry; Glycoside Hydrolase Inhibitors - pharmacology; Inhibitors; Inhibitory Concentration 50; MFTA; QSAR; Quantitative Structure-Activity Relationship; α-Glucosidase; MFTA; Inhibitors; α-Glucosidase; Butyrylcholinesterase; QSAR
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2014.04.018

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.
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•Identified compounds with dual inhibition of enzymes α-glucosidase and butyrylcholinesterase.•Quantitative structure–activity relationships and the common pharmacophore patterns validated the inhibitors.•Computationally revealed the concept of a link existing between type-2 diabetes mellitus and Alzheimer's disease.•Findings will be instrumental for rational design of drug candidates for both of these conditions.