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Aug, 2022;26 (4): 1995-2009.

Design and synthesis of phenoxymethybenzoimidazole incorporating different aryl thiazole-triazole acetamide derivatives as α-glycosidase inhibitors.

Anita Nasli Esfahani, Aida Iraji, Amir Alamir, Shahram Moradi, Mohammad Sadegh Asgari, Samanesadat Hosseini, Somayeh Mojtabavi, Ensieh Nasli-Esfahani, Mohammad Ali Faramarzi, Fatemeh Bandarian, Bagher Larijani, Haleh Hamedifar, Mir Hamed Hajimiri, Mohammad Mahdavi
Author Information
  1. Anita Nasli Esfahani: Department of Chemistry Tehran North Branch, Islamic Azad University, Tehran, Iran.
  2. Aida Iraji: Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
  3. Amir Alamir: Department of Chemistry Tehran North Branch, Islamic Azad University, Tehran, Iran.
  4. Shahram Moradi: Department of Chemistry Tehran North Branch, Islamic Azad University, Tehran, Iran.
  5. Mohammad Sadegh Asgari: Department of Chemistry, Iran University of Science and Technology, Tehran, Iran.
  6. Samanesadat Hosseini: Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  7. Somayeh Mojtabavi: Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and Biotechnology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
  8. Ensieh Nasli-Esfahani: Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
  9. Mohammad Ali Faramarzi: Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and Biotechnology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
  10. Fatemeh Bandarian: Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
  11. Bagher Larijani: Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
  12. Haleh Hamedifar: CinnaGen Medical Biotechnology Research Center, Alborz University of Medical Sciences, Karaj, Iran.
  13. Mir Hamed Hajimiri: Nano Alvand Company, Tehran University of Medical Sciences, Avicenna Tech Park, 1439955991, Tehran, Iran. h.hajimiri@nanoalvand.com.
  14. Mohammad Mahdavi: Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. mahdavi.chem@gmail.com. ORCID
PMID: 34515954 DOI: 10.1007/s11030-021-10310-7

Abstract

A novel series of phenoxymethybenzoimidazole derivatives (9a-n) were rationally designed, synthesized, and evaluated for their α-glycosidase inhibitory activity. All tested compounds displayed promising α-glycosidase inhibitory potential with IC values in the range of 6.31 to 49.89 μM compared to standard drug acarbose (IC = 750.0 ± 10.0 μM). Enzyme kinetic studies on 9c, 9g, and 9m as the most potent compounds revealed that these compounds were uncompetitive inhibitors into α-glycosidase. Docking studies confirmed the important role of benzoimidazole and triazole rings of the synthesized compounds to fit properly into the α-glycosidase active site. This study showed that this scaffold can be considered as a highly potent α-glycosidase inhibitor.

Keywords

Benzimidazole Enzyme inhibition Synthesis Triazole-acetamide α-Glycosidase

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MeSH Term

Acetamides
Glycoside Hydrolase Inhibitors
Kinetics
Molecular Docking Simulation
Molecular Structure
Structure-Activity Relationship
Thiazoles
Triazoles
alpha-Glucosidases

Chemicals

Acetamides
Glycoside Hydrolase Inhibitors
Thiazoles
Triazoles
alpha-Glucosidases
Journal Article

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