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Design, Synthesis, Molecular Docking, and in Vitro Α-Glucosidase Inhibitory Activities of Novel 3-Amino-2,4-Diarylbenzo[4,5]Imidazo[1,2-A]Pyrimidines Against Yeast and Rat Α-Glucosidase Publisher Pubmed



Peytam F1 ; Takalloobanafshi G2 ; Saadattalab T3 ; Norouzbahari M4 ; Emamgholipour Z3 ; Moghimi S1 ; Firoozpour L1 ; Bijanzadeh HR5 ; Faramarzi MA6 ; Mojtabavi S6 ; Rashidiranjbar P2 ; Karima S7 ; Pakraad R7 ; Foroumadi A1, 3
Authors
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Authors Affiliations
  1. 1. Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
  2. 2. School of Chemistry, College of Science, University of Tehran, Tehran, Iran
  3. 3. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Faculty of Medicine, Eastern Mediterranean University, via Mersin 10, Famagusta, Cyprus
  5. 5. Department of Environmental Sciences, Faculty of Natural Resources and Marine Sciences, Tarbiat Modares University, Tehran, Iran
  6. 6. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran

Source: Scientific Reports Published:2021


Abstract

In an attempt to find novel, potent α-glucosidase inhibitors, a library of poly-substituted 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines 3a–ag have been synthesized through heating a mixture of 2-aminobenzimidazoles 1 and α-azidochalcone 2 under the mild conditions. This efficient, facile protocol has been resulted into the desirable compounds with a wide substrate scope in good to excellent yields. Afterwards, their inhibitory activities against yeast α-glucosidase enzyme were investigated. Showing IC50 values ranging from 16.4 ± 0.36 µM to 297.0 ± 1.2 µM confirmed their excellent potency to inhibit α-glucosidase which encouraged us to perform further studies on α-glucosidase enzymes obtained from rat as a mammal source. Among various synthesized 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines, compound 3k exhibited the highest potency against both Saccharomyces cerevisiae α-glucosidase (IC50 = 16.4 ± 0.36 μM) and rat small intestine α-glucosidase (IC50 = 45.0 ± 8.2 μM). Moreover, the role of amine moiety on the observed activity was studied through substituting with chlorine and hydrogen resulted into a considerable deterioration on the inhibitory activity. Kinetic study and molecular docking study have confirmed the in-vitro results. © 2021, The Author(s).
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