Design,synthesis and pharmacological evaluation of chalcone derivatives as acetylcholinesterase inhibitors |
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| Institution: | 1. College of Chemistry and Chemical Engineering, Hu’nan University, Changsha 410082, China;2. College of Pharmacy, Hu’nan University of Traditional Chinese Medicine (TCM), Changsha 410208, China;1. Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Department of Inorganic and Organic Chemistry, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic;2. University of Jan Evangelista Purkynje, Faculty of Science, Department of Chemistry, Ceske mladeze 8, 400 96 Usti nad Labem, Czech Republic;3. University of Defence, Faculty of Military Health Sciences, Department of Toxicology and Center of Advanced Studies, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic;4. Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Department of Pharmaceutical Chemistry and Drug Control, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic;5. University Hospital, Biomedical Research Centre, Sokolska 581, 500 05 Hradec Kralove, Czech Republic;6. University of Hradec Kralove, Faculty of Science, Department of Chemistry, Rokitanskeho 62, 50003 Hradec Kralove, Czech Republic;1. Laboratoire de Synthèse Organique et Molécules Bioactives, Université de Strasbourg/CNRS (UMR 7509), Ecole Européenne de Chimie, Polymères et Matériaux, 25 rue Becquerel, 67087 Strasbourg, France;2. Institut Universitaire de France, 103 Bd Saint-Michel, 75005 Paris, France;3. ICSN-CNRS (Bat. 27)—LabEx LERMIT, 1, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France;4. ICOA, UMR 7311, Université d’Orléans et CNRS, rue de Chartres, BP 6759, 45067 Orléans, France;1. Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad-22060, Abbottabad, Pakistan;2. Division of Analytical Chemistry, Institute of Chemical Science, Bahauddin Zakariya University, 60800, Multan, Pakistan;3. Institute of Chemistry, University of the Punjab, Lahore, Pakistan;1. Institute of Chemistry, University of the Punjab, Lahore 54590, Pakistan;2. Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan;3. Department of Biochemistry & Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan;4. Institute of Molecular Sciences & Bioinformatics, Lahore 54000, Pakistan;1. Department of Chemistry, Quaid-I-Azam University, Islamabad, Pakistan;2. Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan;3. Structural Bioinformatics Team, Division of Structural and Synthetic Biology, Center for Life Science Technologies, RIKEN, 1-7-22 Suehiro, Yokohama, Kanagawa 230-0045, Japan;4. Department of Biosciences, COMSATS Institute of Information Technology, Park Road, Islamabad, Pakistan |
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| Abstract: | A novel series of chalcone derivatives (4a–8d) were designed, synthesized, and evaluated for the inhibition activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The log P values of the compounds were shown to range from 1.49 to 2.19, which suggested that they were possible to pass blood brain barriers in vivo. The most promising compound 4a (IC50: 4.68 μmol/L) was 2-fold more potent than Rivastigmine against AChE (IC50: 10.54 μmol/L) and showed a high selectivity for AChE over BuChE (ratio: 4.35). Enzyme kinetic study suggested that the inhibition mechanism of compound 4a was a mixed-type inhibition. Meanwhile, the result of molecular docking showed its potent inhibition of AChE and high selectivity for AChE over BuChE. |
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| Keywords: | Chalcone derivatives AChE inhibitors Molecular docking |
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