Synthesis and bio-evaluation of new multifunctional methylindolinone-1,2,3-triazole hybrids as anti-Alzheimer's agents

• Published in: Journal of molecular structure 2021-04, Vol.1229, p.129828, Article 129828
• Main Authors: Saeedi, Mina, Maleki, Atefeh, Iraji, Aida, Hariri, Roshanak, Akbarzadeh, Tahmineh, Edraki, Najmeh, Firuzi, Omidreza, Mirfazli, Seyedeh Sara
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Cholinesterase; Methylindolinone; Neuroprotection; Synthesis; Triazole
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2020.129828

•14 new methylindoline-triazole hybrids were designed and synthesized as anti-Alzheimer agents.•In vitro biological evaluations and structure-activity relationships of the resulting compounds were established.•Compound 7k was a potent selective butyrycholinesterase inhibitor.•7k demonstrated significant protective effect on Aβ-induced neuronal injury.•Docking study revealed stable interactions of 7k with butyrycholinesterase. In view of the multifactorial nature of Alzheimer's disease, a new series of methylindolinone-1,2,3-triazole derivatives (7a-n) were efficiently prepared and evaluated for their in vitro cholinesterase inhibitory activity. Although most synthesized compounds showed weak acetylcholinesterase inhibitory activity, they depicted moderate to good activity against butyrylcholinesterase. The IC50 value for anti-BuChE activity of compound 7k was calculated as 4.78 μM which was more potent than the reference drug donepezil (5.19 μM). Based on the molecular docking evaluation, it was found that compound 7k could bind simultaneously to the peripheral and catalytic sites of BuChE. Also, the optimal compound 7k was further assessed as a BACE1 inhibitor and neuroprotective agent. [Display omitted]