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Homogeneous Time-resolved Förster Resonance Energy Transfer-based Assay for Detection of Insulin Secretion
Published on: May 10, 2018
Nicotinic Acid Derivatives As Novel Noncompetitive α-Amylase and α-Glucosidase Inhibitors for Type 2 Diabetes
Andrea Citarella1, Miriam Cavinato2, Elena Rosini3
1Department of Chemistry, University of Milan, Via Golgi 19 20133 Milano, Italy.
Abstract:
A library of novel nicotinic acid derivatives, focusing on the modification of position 6 of the pyridine ring with (thio)ether functionalities, was mostly produced through an innovative green synthetic approach (Cyrene-based) and evaluated for their α-amylase and α-glucosidase inhibitory activity. Compounds 8 and 44 demonstrated micromolar inhibition against α-amylase (IC50 of 20.5 and 58.1 μM, respectively), with 44 exhibiting a remarkable ∼72% enzyme inactivation level, surpassing the efficacy of the control compound, acarbose. Conversely, 35 and 39 exhibited comparable inhibition values to acarbose against α-glucosidase (IC50 of 32.9 and 26.4 μM, respectively) and a significant enhancement in enzyme inhibition at saturation (∼80-90%). Mechanistic studies revealed that the most promising compounds operated through a noncompetitive inhibition mechanism for both α-amylase and α-glucosidase, offering advantages for function regulation over competitive inhibitors. These inhibitors may open a new perspective for the development of improved hypoglycemic agents for type 2 diabetes treatment.
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