Aryl-quinoline-4-carbonyl hydrazone bearing different 2-methoxyphenoxyacetamides as potent α-glucosidase inhibitors; molecular dynamics, kinetic and structure-activity relationship studies

  • Sci Rep. 2024 Jan 3;14(1):388. doi: 10.1038/s41598-023-50395-8.
Haleh Hamedifar  1  2 ,  Mahroo Mirfattahi  3 ,  Minoo Khalili Ghomi  3 ,  Homa Azizian  4 ,  Aida Iraji  5  6 ,  Milad Noori  7 ,  Ali Moazzam  3 ,  Navid Dastyafteh  7 ,  Ali Nokhbehzaim  8 ,  Katayoun Mehrpour  5  6 ,  Shahrzad Javanshir  7 ,  Somayeh Mojtabavi  9 ,  Mohammad Ali Faramarzi  9 ,  Bagher Larijani  3 ,  Mir Hamed Hajimiri  10 ,  Mohammad Mahdavi  11
Affiliations
  • 1. CinnaGen Medical Biotechnology Research Center, Alborz University of Medical Sciences, Karaj, Iran.
  • 2. CinnaGen Research and Production Co., Alborz, Iran.
  • 3. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
  • 4. Department of Medicinal Chemistry, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran.
  • 5. Research Center for Traditional Medicine and History of Medicine, Department of Persian Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, 7134845794, Iran.
  • 6. Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
  • 7. Pharmaceutical and Heterocyclic Chemistry Research Laboratory, Department of Chemistry, Iran University of Science and Technology, Tehran, 16846-13114, Iran.
  • 8. Student Research Committee, Alborz University of Medical Sciences, Karaj, Iran.
  • 9. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and Biotechnology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
  • 10. Nano Alvand Company, Avicenna Tech Park, Tehran University of Medical Sciences, Tehran, 1439955991, Iran. [email protected].
  • 11. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. [email protected].
PMID: 38172167 DOI: 10.1038/s41598-023-50395-8
Abstract

Regarding the important role of α-glucosidase enzyme in the management of type 2 diabetes mellitus, the current study was established to design and synthesize aryl-quinoline-4-carbonyl hydrazone bearing different 2-methoxyphenoxyacetamide (11a-o) and the structure of all derivatives was confirmed through various techniques including IR, 1H-NMR, 13C-NMR and elemental analysis. Next, the α-glucosidase inhibitory potentials of all derivatives were evaluated, and all compounds displayed potent inhibition with IC50 values in the range of 26.0 ± 0.8-459.8 ± 1.5 µM as compared to acarbose used as control, except 11f and 11l. Additionally, in silico-induced fit docking and molecular dynamics studies were performed to further investigate the interaction, orientation, and conformation of the newly synthesized compounds over the active site of α-glucosidase.

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