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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
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Authors Affiliations
  1. 1. Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  4. 4. Central Research Laboratory, Shiraz University of Medical Sciences, Shiraz, Iran
  5. 5. Pharmaceutical and Heterocyclic Chemistry Research Laboratory, Department of Chemistry, Iran University of Science and Technology, Tehran, 16846-13114, Iran
  6. 6. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and Biotechnology Research Center, Tehran University of Medical Sciences, Tehran, Iran

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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