Dual inhibition of the α-glucosidase and butyrylcholinesterase studied by molecular field topology analysis.
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.
Department of Chemistry, University of Florida, PO Box 117200, Gainesville, FL 32611, USA; Department of Chemistry, Quaid i Azam University, Islamabad 45320, Pakistan.
Farukh
F
Jabeen
Department of Chemistry, University of Florida, PO Box 117200, Gainesville, FL 32611, USA.
Polina V
PV
Oliferenko
Department of Chemistry, University of Florida, PO Box 117200, Gainesville, FL 32611, USA.
Alexander A
AA
Oliferenko
Department of Chemistry, University of Florida, PO Box 117200, Gainesville, FL 32611, USA; Department of Chemistry, University of Tartu, Tartu 50411, Estonia.
Girinath G
GG
Pillai
Department of Chemistry, Quaid i Azam University, Islamabad 45320, Pakistan.
Farzana Latif
FL
Ansari
Department of Chemistry, University of Florida, PO Box 117200, Gainesville, FL 32611, USA. Electronic address: charlesdennishall@gmail.com.
C Dennis
CD
Hall
Department of Chemistry, University of Florida, PO Box 117200, Gainesville, FL 32611, USA. Electronic address: Katritzky@chem.ufl.edu.
Alan R
AR
Katritzky
D002091:Butyrylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D065089:Glycoside Hydrolase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D021281:Quantitative Structure-Activity Relationship; D000520:alpha-Glucosidases / Q000378:metabolism*
D002800:Cholinesterase Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D002091:Butyrylcholinesterase; D000520:alpha-Glucosidases
Butyrylcholinesterase; Inhibitors; MFTA; QSAR; α-Glucosidase