Design, Synthesis and Biological Evaluation of Novel Triazole N-acylhydrazone Hybrids for Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder that involves different pathogenic mechanisms. In this regard, the goal of this study was the design and synthesis of new compounds with multifunctional pharmacological activity by molecular hybridization of structural fragments of curcumin and resveratrol connected by an N-acyl-hydrazone function linked to a 1,4-disubstituted triazole system. Among these hybrid compounds, derivative 3e showed the ability to inhibit acetylcholinesterase activity, the intracellular formation of reactive oxygen species as well as the neurotoxicity elicited by Aβ42 oligomers in neuronal SH-SY5Y cells. In parallel, compound 3e showed a good profile of safety and ADME parameters. Taken together, these results suggest that 3e could be considered a lead compound for the further development of AD therapeutics.

Inhibitory potential of nitrogen, oxygen and sulfur containing heterocyclic scaffolds against acetylcholinesterase and butyrylcholinesterase

“…This compound also showed a good safety profile in the same neuronal model and in silico ADME parameters. Taken together, these results suggest that compound 143 could be considered as a lead compound for the development of further AD therapeutics 222 ( Table 5 ).…”

Anticancer agents incorporating the N‐acylhydrazone scaffold: Progress from 2017 to present

“…[13][14][15][16][17][18][19] Several studies on the chemistry and bioactivity of N-acylhydrazone lead scaffold have been published recently. This topic has gained significance over time for the development of novel, therapeutically effective bioactive N-acylhydrazone candidates as anticancer, [20][21][22][23] anti-inflammatory, [24][25][26][27][28][29][30][31] anti-Alzheimer, [32][33][34][35] antimicrobial agents, [36][37][38][39][40] and more. N-Acylhydrazones continue to be a prominent topic in therapeutic research, especially when it comes to the treatment of cancer.…”

Click-designed vanilloid-triazole conjugates as dual inhibitors of AChE and Aβ aggregation

“…21 Furthermore, several triazole-based compounds were reported as promising inhibitors against AD. [22][23][24][25] In this context, we are encouraged to design new 1,2,3triazole-conjugates of vanilloids and investigate their neuroprotective activity against AD. The molecular docking technique was utilized to anticipate the docking scores and poses of the most potent triazole esters 9 and 8 with AChE and Ab40/42.…”