Design, Synthesis, and Biological Evaluation of Molecular Hybrids Incorporating Coumarin-Pyrazole-Linked Indolinone Derivatives With Antioxidant and Anti-Alzheimer Properties.
7 affiliations
- 1Chemistry of Natural Compounds Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Cairo, Egypt.
- 2Biochemistry Department, Biotechnology Research Institute, National Research Centre, Giza, Egypt.
- 3Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sinai University, Kantara branch, Ismailia, Egypt.
- 4Pediatric Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
- 5Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
- 6School of Pharmacy, Fudan University, Shanghai, China.
- 7Department of Therapeutic Chemistry, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Cairo, Egypt.
Abstract
The increase in global life expectancy has resulted in a significant rise in the occurrence of Alzheimer's disease (AD), making it a critical public health burden. Therefore, there is an urgent need to create effective methods to prevent or slow down the progression of the disease. In this regard, fifteen previously reported hybrid molecules (7a-c, 10a-j, and 13a,b), combining 4-hydroxycoumarin and pyrazolyl indolin-2-one structures, were resynthesized and tested for their antioxidant and anti-Alzheimer properties. Several of these compounds showed moderate to strong biological activity. Among these, compound 7a demonstrated excellent antioxidant capacity (TAC = 80.65 mg gallic acid/g; IRP = 68.90 µg/mL) and impressive free radical scavenging abilities (DPPH = 5.33 µg/mL; ABTS = 4.59 µg/mL; NO = 6.76 µg/mL), comparable to the standard antioxidant ascorbic acid. Additionally, compound 7a demonstrated the robust inhibition of acetylcholinesterase (AChE) with an IC₅₀ of 6.89 µg/mL, as well as potent inhibition of butyrylcholinesterase (BChE) (IC₅₀ = 5.93 µg/mL). Molecular docking analyses of compound 7a revealed favorable binding interactions and stable conformations within the enzyme's active site, supporting its strong inhibitory effect. Overall, these findings indicate that this group of hybrid molecules offers a promising framework for developing new cholinesterase-targeting treatments for AD.
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BibTeX
@article{sabt2026design,
title = {{Design, Synthesis, and Biological Evaluation of Molecular Hybrids Incorporating Coumarin-Pyrazole-Linked Indolinone Derivatives With Antioxidant and Anti-Alzheimer Properties.}},
author = {Ahmed Sabt and Wael Mahmoud Aboulthana and Abdulrahman M Saleh and Hoda Atef Abdelsattar Ibrahim and Asmaa Saleh and Xinsheng Lei and Aladdin M Srour},
journal = {Chemistry \& biodiversity},
year = {2026},
month = nov,
doi = {10.1002/cbdv.71900},
url = {https://europepmc.org/article/MED/42967596},
note = {CC BY},
}
RIS
TY - JOUR
TI - Design, Synthesis, and Biological Evaluation of Molecular Hybrids Incorporating Coumarin-Pyrazole-Linked Indolinone Derivatives With Antioxidant and Anti-Alzheimer Properties.
AU - Ahmed Sabt
AU - Wael Mahmoud Aboulthana
AU - Abdulrahman M Saleh
AU - Hoda Atef Abdelsattar Ibrahim
AU - Asmaa Saleh
AU - Xinsheng Lei
AU - Aladdin M Srour
PY - 2026
DA - 2026/11/01
JO - Chemistry & biodiversity
DO - 10.1002/cbdv.71900
UR - https://europepmc.org/article/MED/42967596
AB - The increase in global life expectancy has resulted in a significant rise in the occurrence of Alzheimer's disease (AD), making it a critical public health burden. Therefore, there is an urgent need to create effective methods to prevent or slow down the progression of the disease. In this regard, fifteen previously reported hybrid molecules (7a-c, 10a-j, and 13a,b), combining 4-hydroxycoumarin and pyrazolyl indolin-2-one structures, were resynthesized and tested for their antioxidant and anti-Alzheimer properties. Several of these compounds showed moderate to strong biological activity. Among these, compound 7a demonstrated excellent antioxidant capacity (TAC = 80.65 mg gallic acid/g; IRP = 68.90 µg/mL) and impressive free radical scavenging abilities (DPPH = 5.33 µg/mL; ABTS = 4.59 µg/mL; NO = 6.76 µg/mL), comparable to the standard antioxidant ascorbic acid. Additionally, compound 7a demonstrated the robust inhibition of acetylcholinesterase (AChE) with an IC₅₀ of 6.89 µg/mL, as well as potent inhibition of butyrylcholinesterase (BChE) (IC₅₀ = 5.93 µg/mL). Molecular docking analyses of compound 7a revealed favorable binding interactions and stable conformations within the enzyme's active site, supporting its strong inhibitory effect. Overall, these findings indicate that this group of hybrid molecules offers a promising framework for developing new cholinesterase-targeting treatments for AD.
SN - 1612-1872
SN - 1612-1880
ER -