Synthesis of new Hantzsch adducts showing Ca2+ channel blockade capacity, cholinesterase inhibition and antioxidant power

Author(s):  
Irene Pachón-Angona ◽  
Maciej Maj ◽  
Artur Wnorowski ◽  
Helene Martin ◽  
Krzysztof Jóźwiak ◽  
...  

Background: Alzheimer’s disease is a chronic neurodegenerative chronic disease with a heavy social and economic impact in our developed societies, which still lacks an efficient therapy. Method: This paper describes the Hantzsch multicomponent synthesis of twelve alkyl hexahydro-quinoline-3-carboxylates, 4a–l, along with the evaluation of their Ca2+ channel blockade capacity, cholinesterase inhibition and antioxidant power. Results: Compound 4l showed submicromolar inhibition of butyrylcholinesterase, Ca2+ channel antagonism and an antioxidant effect. Conclusion: Compound 4l is an interesting compound that deserves further investigation for Alzheimer’s disease therapy.

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3190
Author(s):  
Lazhar Zribi ◽  
Irene Pachòn-Angona ◽  
Òscar M. Bautista-Aguilera ◽  
Daniel Diez-Iriepa ◽  
José Marco-Contelles ◽  
...  

Alzheimer’s disease (AD) is multifactorial disease characterized by the accumulation of abnormal extracellular deposits of amyloid-beta (Aβ) peptide, and intracellular neurofibrillary tangles (NFTs), along with dramatic neuronal death and decreased levels of choline acetyltransferase. Given the limited therapeutic success of available drugs, it is urgent to explore all the opportunities available to combat this illness. Among them, the discovery of new heterocyclic scaffolds binding different receptors involved in AD should offer structural diversity and new therapeutic solutions. In this context, this work describes new triazolopyridopyrimidine easily prepared in good yields showing anticholinesterase inhibition and strong antioxidant power, particularly the most balanced: 6-amino-5-(4-methoxyphenyl)-2-phenyl-[1,2,4]triazolo[1′,5′:1,6] pyrido[2,3-d]pyrimidine-4-carbonitrile(3c) with IC50 equal to 1.32 μM against AChE and oxygen radical absorbance capacity (ORAC) value equal to 4.01 Trolox equivalents (TE); thus representing a new and very promising hit-triazolopyridopyrimidine for AD therapy.


2017 ◽  
Vol 30 (2) ◽  
pp. 128-135 ◽  
Author(s):  
Shakeel Ahmed Ansari ◽  
Rukhsana Satar ◽  
Asma Perveen ◽  
Ghulam Md Ashraf

2017 ◽  
Vol 14 (6) ◽  
Author(s):  
Ondrej Holas ◽  
Jan Korabecny ◽  
Zuzana Gazova ◽  
Katarina Siposova ◽  
Kamil Musilek ◽  
...  

2010 ◽  
Vol 20 (s2) ◽  
pp. S579-S590 ◽  
Author(s):  
Maria Ankarcrona ◽  
Francesca Mangialasche ◽  
Bengt Winblad

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