Design, synthesis of triazole-based scaffolds, N-(substitutedphenyl)-2-(5-(4-methoxyphenyl)-4-phenyl-4H-1,2,4-triazol-3-ylthiol)acetamides: As potential anti-cholinesterase agents for neurodegenerative diseases

• Published in: Journal of Molecular Structure
• Main Author: Siddiqui S.Z.; Arfan M.; Abbasi M.A.; Aziz-ur-Rehman; Shah S.A.A.; Parveen R.; Ashraf M.; Solangi M.; Hussain S.; Khan K.M.
• Format: Article
• Language: English
• Published: Elsevier B.V. 2023
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85160806262&doi=10.1016%2fj.molstruc.2023.135885&partnerID=40&md5=46073bcb625a8f3819b2b439e40d495c
• ISSN: 222860
• DOI: 10.1016/j.molstruc.2023.135885

Alzheimer's disease (AD) is currently regarded as a global health concern; there are now about 50 million AD patients worldwide, and it is predicted that this number will double every five years and reach 152 million by 2050. Although there are therapies that can help with the symptoms of Alzheimer's disease, there is currently no cure for the condition. This study synthesized a series of novel triazole scaffolds 7a–k, fully characterized, and investigated to unravel their anticholinesterase potential. Density functional theory (DFT) calculations were carried out to investigate the compounds' molecular geometry and electron distribution. The significant enzymatic inhibitory potential was exhibited by compound 7c against AChE (IC50 = 9.52 ± 0.25 μM) and 7g against BChE (IC50 = 31.51 ± 0.38 μM), in comparison to the standard drug eserine. Moreover, the compounds were also screened for their anti-proliferative activity against HCT-116 human cancer cell lines, with 7f demonstrating 19.2% cell viability at 25 μM and 28.4% cell viability at 50 μM. The bioactivity results were further validated through computational docking analysis. © 2023