Journal Article Ppublish 2 citations
PubMed: 38864182 DOI: 10.1080/17568919.2024.2359894
Synthesis of novel hybrids of 1,2,3-triazoles-hydrazone: targeting cholinesterases and Alzheimer's related genes.
Future Med Chem 16(15):1519-1535
Authors: Diba Shareghi-Boroujeni, Aida Iraji, Mahintaj Dara, Mohammad Hashem Hashempur, Shahrokh Zare, Roshanak Hariri, Tahmineh Akbarzadeh, Mina Saeedi
Affiliations
- Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
- Research Center for Traditional Medicine & History of Medicine, Department of Persian Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
- Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
- Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
- Persian Medicine & Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Abstract
Aim: A new series of 1,2,3-triazole-hydrazone derivatives were developed to evaluate their anti-Alzheimer's activity. Materials & methods: 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 GSK-3α, GSK-3β, DYRK1 and CDK5 were assessed in the presence of compounds 6m and 6p.Results:6m and 6p; acting as mixed-type inhibitors, exhibited promising acetylcholinesterase and butyrylcholinesterase inhibitory activity, respectively. 6m demonstrated no toxicity under tested concentrations on the SH-SY5Y cells and positively impacted neurodegenerative pathways. Notably, 6m displayed a significant downregulation in mRNA levels of GSK-3α, GSK-3β and CDK5.Conclusion: The target compounds could be considered in developing anti-Alzheimer's disease agents.
MeSH
Cells, Cholinesterases, Hydrazones, Genes, Chemistry, Pharmaceutical, Triazoles