Novel 3-phenylcoumarin–lipoic acid conjugates as multi-functional agents for potential treatment of Alzheimer's disease

Leili Jalili-Baleh, Hamid Nadri, Hamid Forootanfar, Alireza Samzadeh-Kermani, Tuba Tüylü Küçükkılınç, Beyza Ayazgok, Mahban Rahimifard, Maryam Baeeri, Mohsen Doostmohammadi, Loghman Firoozpour, Bukhari Syed Nasir Abbas, Mohammad Abdollahi, Mohammad Reza Ganjali, Saeed Emami, Mehdi Khoobi, Alireza Foroumadi

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

New series of triazole-containing 3-phenylcoumarin–lipoic acid conjugates were designed as multi-functional agents for treatment of Alzheimer's disease. The target compounds 4a-o were synthesized via the azide-alkyne cycloaddition reaction and their biological activities were primarily evaluated in terms of neuroprotection against H2O2-induced cell death in PC12 cells and AChE/BuChE inhibition. The promising compounds 4j and 4i containing four carbons spacer were selected for further biological evaluations. Based on the obtained results, the benzocoumarin derivative 4j with IC50 value of 7.3 µM was the most potent AChE inhibitor and displayed good inhibition toward intracellular reactive oxygen species (ROS). This compound with antioxidant and metal chelating ability showed also protective effect on cell injury induced by Aβ1-42 in SH-SY5Y cells. Although the 8-methoxycoumarin analog 4i was slightly less active than 4j against AChE, but displayed higher protection ability against H2O2-induced cell death in PC12 and could significantly block Aβ-aggregation. The results suggested that the prototype compounds 4i and 4j might be promising multi-functional agents for the further development of the disease-modifying treatments of Alzheimer's disease.

Original languageEnglish
Pages (from-to)223-234
Number of pages12
JournalBioorganic Chemistry
Volume79
DOIs
Publication statusPublished - 1 Sep 2018
Externally publishedYes

Fingerprint

Aptitude
Alzheimer Disease
Cell Death
Cell death
Acids
Triazoles
Alkynes
Azides
PC12 Cells
Cycloaddition Reaction
Inhibitory Concentration 50
Reactive Oxygen Species
Carbon
Cycloaddition
Antioxidants
Metals
Chelation
Bioactivity
Wounds and Injuries
Agglomeration

Keywords

  • Alzheimer's disease
  • Amyloid beta
  • Antioxidant
  • Coumarin
  • Lipoic acid
  • Neuroprotective activity

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Drug Discovery
  • Organic Chemistry

Cite this

Jalili-Baleh, L., Nadri, H., Forootanfar, H., Samzadeh-Kermani, A., Küçükkılınç, T. T., Ayazgok, B., ... Foroumadi, A. (2018). Novel 3-phenylcoumarin–lipoic acid conjugates as multi-functional agents for potential treatment of Alzheimer's disease. Bioorganic Chemistry, 79, 223-234. https://doi.org/10.1016/j.bioorg.2018.04.030

Novel 3-phenylcoumarin–lipoic acid conjugates as multi-functional agents for potential treatment of Alzheimer's disease. / Jalili-Baleh, Leili; Nadri, Hamid; Forootanfar, Hamid; Samzadeh-Kermani, Alireza; Küçükkılınç, Tuba Tüylü; Ayazgok, Beyza; Rahimifard, Mahban; Baeeri, Maryam; Doostmohammadi, Mohsen; Firoozpour, Loghman; Syed Nasir Abbas, Bukhari; Abdollahi, Mohammad; Ganjali, Mohammad Reza; Emami, Saeed; Khoobi, Mehdi; Foroumadi, Alireza.

In: Bioorganic Chemistry, Vol. 79, 01.09.2018, p. 223-234.

Research output: Contribution to journalArticle

Jalili-Baleh, L, Nadri, H, Forootanfar, H, Samzadeh-Kermani, A, Küçükkılınç, TT, Ayazgok, B, Rahimifard, M, Baeeri, M, Doostmohammadi, M, Firoozpour, L, Syed Nasir Abbas, B, Abdollahi, M, Ganjali, MR, Emami, S, Khoobi, M & Foroumadi, A 2018, 'Novel 3-phenylcoumarin–lipoic acid conjugates as multi-functional agents for potential treatment of Alzheimer's disease', Bioorganic Chemistry, vol. 79, pp. 223-234. https://doi.org/10.1016/j.bioorg.2018.04.030
Jalili-Baleh L, Nadri H, Forootanfar H, Samzadeh-Kermani A, Küçükkılınç TT, Ayazgok B et al. Novel 3-phenylcoumarin–lipoic acid conjugates as multi-functional agents for potential treatment of Alzheimer's disease. Bioorganic Chemistry. 2018 Sep 1;79:223-234. https://doi.org/10.1016/j.bioorg.2018.04.030
Jalili-Baleh, Leili ; Nadri, Hamid ; Forootanfar, Hamid ; Samzadeh-Kermani, Alireza ; Küçükkılınç, Tuba Tüylü ; Ayazgok, Beyza ; Rahimifard, Mahban ; Baeeri, Maryam ; Doostmohammadi, Mohsen ; Firoozpour, Loghman ; Syed Nasir Abbas, Bukhari ; Abdollahi, Mohammad ; Ganjali, Mohammad Reza ; Emami, Saeed ; Khoobi, Mehdi ; Foroumadi, Alireza. / Novel 3-phenylcoumarin–lipoic acid conjugates as multi-functional agents for potential treatment of Alzheimer's disease. In: Bioorganic Chemistry. 2018 ; Vol. 79. pp. 223-234.
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