| Title : Chromone-lipoic acid conjugate: Neuroprotective agent having acceptable butyrylcholinesterase inhibition, antioxidant and copper-chelation activities - Jalili-Baleh_2021_Daru__ |
| Author(s) : Jalili-Baleh L , Nadri H , Forootanfar H , Tuylu Kucukkilinc T , Ayazgok B , Sharifzadeh M , Rahimifard M , Baeeri M , Abdollahi M , Foroumadi A , Khoobi M |
| Ref : Daru , : , 2021 |
|
Abstract :
PURPOSE: Alzheimer's disease (AD) is a multifaceted neurodegenerative disease. To target simultaneously multiple pathological processes involved in AD, natural-origin compounds with unique characteristics are promising scaffolds to develop novel multi-target compounds in the treatment of different neurodegenerative disease, especially AD. In this study, novel chromone-lipoic acid hybrids were prepared to find a new multifunctional lead structure for the treatment of AD. METHODS: Chromone-lipoic acid hybrids were prepared through click reaction and their neuroprotection and anticholinesterase activity were fully evaluated. The anti-amyloid aggregation, antioxidant and metal-chelation activities of the best compound were also investigated by standard methods to find a new multi-functional agent against AD. RESULTS: The primary biological screening demonstrated that all compounds had significant neuroprotection activity against H2O2-induced cell damage in PC12 cells. Compound 19 as the most potent butyrylcholinesterase (BuChE) inhibitor (IC50 = 7.55 microM) having significant neuroprotection activity as level as reference drug was selected for further biological evaluations. Docking and kinetic studies revealed non-competitive mixed-type inhibition of BuChE by compound 19. It could significantly reduce formation of the intracellular reactive oxygen species (ROS) and showed excellent reducing power (85.57 mM Fe+2), comparable with quercetin and lipoic acid. It could also moderately inhibit Abeta aggregation and selectively chelate with copper ions in 2:1 M ratio. CONCLUSION: Compound 19 could be considered as a hopeful multifunctional agent for the further development gainst AD owing to the acceptable neuroprotective and anti-BuChE activity, moderate anti-Abeta aggregation activity, outstanding antioxidant activity as well as selective copper chelation ability. A new chromone-lipoic acid hybrid was synthesized as anti-Alzheimer agent with BuChE inhibitory activity, anti-Abeta aggregation, metal-chelation and antioxidant properties. |
| PubMedSearch : Jalili-Baleh_2021_Daru__ |
| PubMedID: 33420969 |
Jalili-Baleh L, Nadri H, Forootanfar H, Tuylu Kucukkilinc T, Ayazgok B, Sharifzadeh M, Rahimifard M, Baeeri M, Abdollahi M, Foroumadi A, Khoobi M (2021)
Chromone-lipoic acid conjugate: Neuroprotective agent having acceptable butyrylcholinesterase inhibition, antioxidant and copper-chelation activities
Daru
:
Jalili-Baleh L, Nadri H, Forootanfar H, Tuylu Kucukkilinc T, Ayazgok B, Sharifzadeh M, Rahimifard M, Baeeri M, Abdollahi M, Foroumadi A, Khoobi M (2021)
Daru
: