Nicotinic Acid Derivatives As Novel Noncompetitive α-Amylase and α-Glucosidase Inhibitors for Type 2 Diabetes Treatment
Articolo
Data di Pubblicazione:
2024
Citazione:
Nicotinic Acid Derivatives As Novel Noncompetitive α-Amylase and α-Glucosidase Inhibitors for Type 2 Diabetes Treatment / A. Citarella, M. Cavinato, E. Rosini, H. Shehi, F. Ballabio, C. Camilloni, V. Fasano, A. Silvani, D. Passarella, L. Pollegioni, M. Nardini. - In: ACS MEDICINAL CHEMISTRY LETTERS. - ISSN 1948-5875. - 15:9(2024), pp. 1474-1481. [10.1021/acsmedchemlett.4c00190]
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 alpha-amylase and alpha-glucosidase inhibitory activity. Compounds 8 and 44 demonstrated micromolar inhibition against alpha-amylase (IC50 of 20.5 and 58.1 mu M, respectively), with 44 exhibiting a remarkable similar to 72% enzyme inactivation level, surpassing the efficacy of the control compound, acarbose. Conversely, 35 and 39 exhibited comparable inhibition values to acarbose against alpha-glucosidase (IC50 of 32.9 and 26.4 mu M, respectively) and a significant enhancement in enzyme inhibition at saturation (similar to 80-90%). Mechanistic studies revealed that the most promising compounds operated through a noncompetitive inhibition mechanism for both alpha-amylase and alpha-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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
synthesis; nicotinic acid; enzyme inhibitors; medicinal chemistry; organic chemistry;
Elenco autori:
A. Citarella, M. Cavinato, E. Rosini, H. Shehi, F. Ballabio, C. Camilloni, V. Fasano, A. Silvani, D. Passarella, L. Pollegioni, M. Nardini
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