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Synthesis, in Vitro Inhibitor Screening, Structure–Activity Relationship, and Molecular Dynamic Simulation Studies of Novel Thioquinoline Derivatives As Potent Α-Glucosidase Inhibitors Publisher Pubmed



Forozan RD1 ; Ghomi MK2 ; Iraji A3, 4 ; Montazer MN2 ; Noori M5 ; Dastyafteh N5 ; Mojtabavi S6 ; Faramarzi MA6 ; Sadatebrahimi SE1 ; Larijani B2 ; Javanshir S5 ; Mahdavi M2
Authors

Source: Scientific Reports Published:2023


Abstract

New series of thioquinoline structures bearing phenylacetamide 9a–p were designed, synthesized and the structure of all derivatives was confirmed using different spectroscopic techniques including FTIR, 1H-NMR, 13C-NMR, ESI–MS and elemental analysis. Next, the α-glucosidase inhibitory activities of derivatives were also determined and all the synthesized compounds (IC50 = 14.0 ± 0.6–373.85 ± 0.8 μM) were more potent than standard inhibitors acarbose (IC50 = 752.0 ± 2.0 μM) against α-glucosidase. Structure–activity relationships (SARs) were rationalized by analyzing the substituents effects and it was shown that mostly, electron-donating groups at the R position are more favorable compared to the electron-withdrawing group. Kinetic studies of the most potent derivative, 9m, carrying 2,6-dimethylphenyl exhibited a competitive mode of inhibition with Ki value of 18.0 µM. Furthermore, based on the molecular dynamic studies, compound 9m depicted noticeable interactions with the α-glucosidase active site via several H-bound, hydrophobic and hydrophilic interactions. These interactions cause interfering catalytic potential which significantly decreased the α-glucosidase activity. © 2023, The Author(s).
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