Channar_2017_Biomed.Pharmacother_94_499

Ten fused heterocyclic derivatives bearing the 2,6-di(subsituted phenyl)thiazolo[3,2-b]-1,2,4-triazoles as central rings were synthesized and structures of the compounds were established by analytical and spectral data using FTIR, EI-MS, 1H NMR and 13C NMR techniques. In vitro inhibitory activities of synthesized compounds on alpha-amylase, alpha-glucosidase and alpha-burylcholinesterase (alpha-BuChE) were evaluated using a purified enzyme assays. Compound 5c demonstrated strong and selective alpha-amylase inhibitory activity (IC50=1.1mumol/g). 5g exhibited excellent inhibition against alpha-glucosidase (IC50=1.2mumol/g) when compared with acarbose (IC50=4.7mumol/g) as a positive reference. Compound 5i was found to be most potent derivative against alpha-BuChE with the IC50 of 1.5mumol/g which was comparable to the value obtained for (4.7mumol/g) positive control (i.e. galantamine hydrobromide). Molecular dockings of synthesized compounds into the binding sites of human pancreatic alpha-amylase, intestinal maltase-glucoamylase and neuronal alpha-butrylcholinesterase allowed to shed light on the affinity and binding mode of these novel inhibitors. Preliminary structure-activity relationship (SAR) studies were carried out to understand the relationship between molecular structural features and inhibition activities of synthesized derivatives. These data suggested that compounds 5c, 5g and 5i are promising candidates for hitto- lead follow-up in the drug-discovery process for the treatment of Alzheimer's disease and hyperinsulinamia.