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Design, Synthesis and Evaluation of Novel Multi-Target-Directed Ligands for Treatment of Alzheimer's Disease Based on Coumarin and Lipoic Acid Scaffolds Publisher Pubmed



Jalilibaleh L1 ; Forootanfar H2 ; Kucukkilinc TT3 ; Nadri H4 ; Abdolahi Z4 ; Ameri A5 ; Jafari M2 ; Ayazgok B3 ; Baeeri M1 ; Rahimifard M1 ; Abbas Bukhari SN6 ; Abdollahi M1 ; Ganjali MR7, 8 ; Emami S9 Show All Authors
Authors
  1. Jalilibaleh L1
  2. Forootanfar H2
  3. Kucukkilinc TT3
  4. Nadri H4
  5. Abdolahi Z4
  6. Ameri A5
  7. Jafari M2
  8. Ayazgok B3
  9. Baeeri M1
  10. Rahimifard M1
  11. Abbas Bukhari SN6
  12. Abdollahi M1
  13. Ganjali MR7, 8
  14. Emami S9
  15. Khoobi M1, 10
  16. Foroumadi A11
Show Affiliations
Authors Affiliations
  1. 1. The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, 1417614411, Iran
  2. 2. Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
  3. 3. Hacettepe University, Faculty of Pharmacy, Department of Biochemistry, Ankara, Turkey
  4. 4. Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
  5. 5. Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
  6. 6. Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Aljouf, Sakaka, 2014, Saudi Arabia
  7. 7. Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  8. 8. Center of Excellence in Electrochemistry, Faculty of Chemistry, University of Tehran, Tehran, Iran
  9. 9. Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
  10. 10. Department of Pharmaceutical Biomaterials, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  11. 11. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Source: European Journal of Medicinal Chemistry Published:2018


Abstract

A novel series of coumarin-lipoic acid conjugates were synthesized via cycloaddition click reaction to find out new multi-target-directed ligands (MTDLs) for treatment of Alzheimer's disease (AD). All of synthesized compounds were screened for neuroprotective and anti-cholinesterase activities. Based on primary screening, two compounds (5 and 11) were subjected to further biological evaluations. In particular, compound 11 which was the most potent AChE inhibitor showed good inhibitory effect on Aβ-aggregation and intracellular ROS (reactive oxygen species) formation, as well as the ability of selective bio-metal chelation and neuroprotection against H2O2- and Aβ1-42-induced cytotoxicity. In the light of these results, the applied hybridization approach introduced new promising lead compound with desired multifunctional properties, being useful in the treatment of Alzheimer's disease. © 2018 Elsevier Masson SAS
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