New Phenylthiosemicarbazide-Phenoxy-1,2,3-Triazole-N-Phenylacetamides As Dual Inhibitors Against Α-Glucosidase and Ptp-1B for the Treatment of Type 2 Diabetes Publisher Pubmed



Ansariashlaghi S¹ ; Fakhrioliaei A¹ ; Mohammadikhanaposhtani M² ; Noori M¹ ; Asadi M³ ; Mojtabavi S⁴ ; Faramarzi MA⁴ ; Esfahani EN⁵ ; Rastegar H⁶ ; Larijani B¹ ; Azizian H³ ; Mahdavi M¹ Show Affiliations
Source: Archiv der Pharmazie Published:2024

Abstract

This study describes the design, synthesis, and evaluation of a novel series of phenylthiosemicarbazide-phenoxy-1,2,3-triazole-N-phenylacetamide derivatives (7a–l) as dual inhibitors of α-glucosidase and protein tyrosine phosphatase 1-B (PTB-1B). The latter enzymes are two important targets in the treatment of type 2 diabetes. The in vitro obtained data demonstrated that all title compounds 7a–l were more potent than the standard inhibitor acarbose against α-glucosidase while only four derivatives (7a, 7g, 7h, and 7h) were more potent than the standard inhibitor suramin against PTP-1B. Furthermore, these data showed that the most potent α-glucosidase inhibitor was compound 7i, with sixfold higher inhibitory activity than acarbose, and the most potent PTP-1B inhibitor was compound 7a with 3.5-fold higher inhibitory activity than suramin. Kinetic studies of compounds 7i and 7a revealed that they inhibited their target enzymes in a competitive mode. The docking study demonstrated that compounds 7i and 7a well occupied the active site pockets of α-glucosidase and PTP-1B, respectively. In silico pharmacokinetic and toxicity assays of the most potent compounds were performed, and the obtained results were compared with those of the standard inhibitors. © 2024 Deutsche Pharmazeutische Gesellschaft.