Synthesis of novel hybrids of 1,2,3-triazoles-hydrazone: targeting cholinesterases and Alzheimer's related genes.

A new series of 1,2,3-triazole-hydrazone derivatives were developed to evaluate their anti-Alzheimer's activity. All compounds were screened toward cholinesterases via the modified Ellman's method. The toxicity assay on SH-SY5Y cells was performed using the MTT assay, and the expression levels of , , and were assessed in the presence of compounds and . and ; acting as mixed-type inhibitors, exhibited promising acetylcholinesterase and butyrylcholinesterase inhibitory activity, respectively. demonstrated no toxicity under tested concentrations on the SH-SY5Y cells and positively impacted neurodegenerative pathways. Notably, displayed a significant downregulation in mRNA levels of , and . The target compounds could be considered in developing anti-Alzheimer's disease agents.