Design, synthesis and evaluation of novel multi-target-directed ligands for treatment of Alzheimer's disease based on coumarin and lipoic acid scaffolds

Leili Jalili-Baleh, Hamid Forootanfar, Tuba Tüylü Küçükkılınç, Hamid Nadri, Zahra Abdolahi, Alieh Ameri, Mandana Jafari, Beyza Ayazgok, Maryam Baeeri, Mahban Rahimifard, Bukhari Syed Nasir Abbas, Mohammad Abdollahi, Mohammad Reza Ganjali, Saeed Emami, Mehdi Khoobi, Alireza Foroumadi

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)600-614
Number of pages15
JournalEuropean Journal of Medicinal Chemistry
Volume152
DOIs
Publication statusPublished - 25 May 2018
Externally publishedYes

Fingerprint

Thioctic Acid
Scaffolds
Alzheimer Disease
Ligands
Lead compounds
Aptitude
Cycloaddition
Cholinesterase Inhibitors
Cycloaddition Reaction
Cytotoxicity
Chelation
Reactive Oxygen Species
Screening
Agglomeration
Metals
coumarin
Neuroprotection
Lead

Keywords

  • Alzheimer's disease
  • Antioxidant
  • Coumarin
  • HDMGQLXNTODMRP-UHFFFAOYSA-N
  • JOGJHTJZUVAOKN-UHFFFAOYSA-N
  • Lipoic acid
  • MTDLs
  • Neuroprotective agents

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Design, synthesis and evaluation of novel multi-target-directed ligands for treatment of Alzheimer's disease based on coumarin and lipoic acid scaffolds. / Jalili-Baleh, Leili; Forootanfar, Hamid; Küçükkılınç, Tuba Tüylü; Nadri, Hamid; Abdolahi, Zahra; Ameri, Alieh; Jafari, Mandana; Ayazgok, Beyza; Baeeri, Maryam; Rahimifard, Mahban; Syed Nasir Abbas, Bukhari; Abdollahi, Mohammad; Ganjali, Mohammad Reza; Emami, Saeed; Khoobi, Mehdi; Foroumadi, Alireza.

In: European Journal of Medicinal Chemistry, Vol. 152, 25.05.2018, p. 600-614.

Research output: Contribution to journalArticle

Jalili-Baleh, L, Forootanfar, H, Küçükkılınç, TT, Nadri, H, Abdolahi, Z, Ameri, A, Jafari, M, Ayazgok, B, Baeeri, M, Rahimifard, M, Syed Nasir Abbas, B, Abdollahi, M, Ganjali, MR, Emami, S, Khoobi, M & Foroumadi, A 2018, 'Design, synthesis and evaluation of novel multi-target-directed ligands for treatment of Alzheimer's disease based on coumarin and lipoic acid scaffolds', European Journal of Medicinal Chemistry, vol. 152, pp. 600-614. https://doi.org/10.1016/j.ejmech.2018.04.058
Jalili-Baleh, Leili ; Forootanfar, Hamid ; Küçükkılınç, Tuba Tüylü ; Nadri, Hamid ; Abdolahi, Zahra ; Ameri, Alieh ; Jafari, Mandana ; Ayazgok, Beyza ; Baeeri, Maryam ; Rahimifard, Mahban ; Syed Nasir Abbas, Bukhari ; Abdollahi, Mohammad ; Ganjali, Mohammad Reza ; Emami, Saeed ; Khoobi, Mehdi ; Foroumadi, Alireza. / Design, synthesis and evaluation of novel multi-target-directed ligands for treatment of Alzheimer's disease based on coumarin and lipoic acid scaffolds. In: European Journal of Medicinal Chemistry. 2018 ; Vol. 152. pp. 600-614.
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AU - Rahimifard, Mahban

AU - Syed Nasir Abbas, Bukhari

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AU - Ganjali, Mohammad Reza

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