Highly efficient, catalyst-free, one-pot sequential four-component synthesis of novel spiroindolinone-pyrazole scaffolds as anti-Alzheimer agents: in silico study and biological screening.

Autor:	Pourtaher H; Department of Chemistry, Faculty of Sciences, Persian Gulf University Bushehr Iran alirezahasaninejad@gmail.com a_hasaninejad@yahoo.com., Mohammadi Y; Research Center for Traditional Medicine and History of Medicine, Department of Persian Medicine, School of Medicine, Shiraz University of Medical Sciences Shiraz 7134845794 Iran aida.iraji@gmail.com iraji@sums.ac.ir.; Stem Cells Technology Research Center, Shiraz University of Medical Sciences Shiraz Iran., Hasaninejad A; Department of Chemistry, Faculty of Sciences, Persian Gulf University Bushehr Iran alirezahasaninejad@gmail.com a_hasaninejad@yahoo.com., Iraji A; Research Center for Traditional Medicine and History of Medicine, Department of Persian Medicine, School of Medicine, Shiraz University of Medical Sciences Shiraz 7134845794 Iran aida.iraji@gmail.com iraji@sums.ac.ir.; Stem Cells Technology Research Center, Shiraz University of Medical Sciences Shiraz Iran.
Jazyk:	angličtina
Zdroj:	RSC medicinal chemistry [RSC Med Chem] 2023 Dec 04; Vol. 15 (1), pp. 207-222. Date of Electronic Publication: 2023 Dec 04 (Print Publication: 2024).
DOI:	10.1039/d3md00255a
Abstrakt:	Alzheimer's disease is a neurodegenerative disorder that impacts memory, thinking, and behavior, and currently, there is no effective cure available for its treatment. This study explored a one-pot strategy for synthesizing spiroindolinone-pyrazole derivatives through a sequential four-component condensation reaction. These derivatives were further investigated for their potential as anti-Alzheimer's disease agents. The developed synthetic procedure provides remarkable advantages, including a clean reaction profile, abundant starting materials, operational simplicity, and easy purification without traditional methods with good to excellent yields (84-96%). Next, the biological potencies of the newly synthesized spiroindolinone-pyrazole derivatives against AChE and BChE as Alzheimer's disease-related targets were determined. Also, the kinetic study and cytotoxicity of the most potent derivative were investigated. Furthermore, molecular docking and molecular dynamics evaluations were performed employing in silico tools to investigate the interaction, orientation, and conformation of the potent analog over the active site of the enzyme. Competing Interests: There are no conflicts to declare. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
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