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ADME properties, bioactivity and molecular docking studies of 4-amino-chalcone derivatives: new analogues for the treatment of Alzheimer, glaucoma and epileptic diseases

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Abstract

In this study, in vitro inhibition effects of (E)-1-(4-aminophenyl)-3-(aryl) prop-2-en-1-one (4-amino-chalcones) derivatives (3a–o) on acetylcholinesterase (AChE) enzyme and human erythrocyte carbonic anhydrase I and II isoenzymes (hCA I- II) were investigated. And also, the biological activities of 4-amino-chalcone derivatives against enzymes which names are acetylcholinesterase (PDB ID: 1OCE), human Carbonic Anhydrase I (PDB ID: 2CAB), human carbonic anhydrase II (PDB ID: 3DC3), were compared. After the results obtained, ADME/T analysis was performed in order to use 4-amino-chalcone derivatives as a drug in the future. Effective inhibitors of carbonic anhydrase I and II isozymes (hCAI and II) and acetylcholinesterase (AChE) enzymes with Ki values in the range of 2.55 ± 0.35–11.75 ± 3.57 nM for hCA I, 4.31 ± 0.78–17.55 ± 5.86 nM for hCA II and 96.01 ± 25.34–1411.41 ± 32.88 nM for AChE, respectively, were the 4-amino-chalcone derivatives (3a–o) molecules.

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Acknowledgements

This work is supported by the Scientific Research Project Fund of Sivas Cumhuriyet University under the project number RGD-020 and ECZ-079. This research was made possible by TUBITAK ULAKBIM, High Performance and Grid Computing Center (TR-Grid e-Infrastructure).

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Arts and Sciences, Tokat Gaziosmanpaşa University, 60250, Tokat, Turkey

    Meliha Burcu Gürdere, Yakup Budak & Mustafa Ceylan

  2. Department of Basic Pharmaceutical Sciences, Division of Biochemistry, Faculty of Pharmacy, Sivas Cumhuriyet University, 58140, Sivas, Turkey

    Umit M. Kocyigit

  3. Department of Biotechnology, Faculty of Science, Bartin University, 74100, Bartin, Turkey

    Parham Taslimi

  4. Department of Chemistry, Faculty of Science, Sivas Cumhuriyet University, 58140, Sivas, Turkey

    Burak Tüzün

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  1. Meliha Burcu Gürdere
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Gürdere, M.B., Budak, Y., Kocyigit, U.M. et al. ADME properties, bioactivity and molecular docking studies of 4-amino-chalcone derivatives: new analogues for the treatment of Alzheimer, glaucoma and epileptic diseases. In Silico Pharmacol. 9, 34 (2021). https://doi.org/10.1007/s40203-021-00094-x

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