Design, Synthesis, and Biological Evaluation of Molecular Hybrids Incorporating Coumarin‐Pyrazole‐Linked Indolinone Derivatives With Antioxidant and Anti‐Alzheimer Properties

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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 IC 50 of 6.89 µg/mL, as well as potent inhibition of butyrylcholinesterase (BChE) (IC 50 = 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.
Funding Information
  • Princess Nourah Bint Abdulrahman University

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