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  3. Design, synthesis, and computational insights into 3-acetyl-8-methoxy coumarin hybrids as potential anti-alzheimer's agents

Design, synthesis, and computational insights into 3-acetyl-8-methoxy coumarin hybrids as potential anti-alzheimer's agents

  • Sci Rep. 2025 Nov 25;15(1):41752. doi: 10.1038/s41598-025-28665-4.
Wajeeha Zareen 1,  Maham Rafique 1,  Nadeem Ahmed 1 2,  Muhammad Ali Khan 1,  Muhammad Tahir 3,  Suraj N Mali 4,  Nastaran Sadeghian 5,  Parham Taslimi 5,  Mostafa A Ismail 6,  Somdatta Y Chaudhari 7,  Ajmal Khan 8 9,  Halil Şenol 10,  Zahid Shafiq 11
Affiliations

Affiliations

  • 1 Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, 60800, Pakistan.
  • 2 College of Chemistry & Chemical Engineering, Central South University, Changsha, 410083, Hunan, China.
  • 3 Hunan Key Laboratory for Super Micro-structure and Ultra-fast Process, School of Physics, Central South University, Changsha, 410083, Hunan, People's Republic of China.
  • 4 Department of Pharmaceutical Chemistry, School of Pharmacy, Dr. D.Y. Patil Deemed to be University, Navi Mumbai, India.
  • 5 Department of Biotechnology, Faculty of Science, Bartin University, 74110, Bartin, Turkey.
  • 6 Department of Chemistry, Faculty of Science, Research Center for Advanced Materials Science (RCAMS), King Khalid University, P.O. Box 960, Abha, 61421, Saudi Arabia.
  • 7 Department of Pharmaceutical Chemistry, Modern College of Pharmacy, Nigdi, Pune, India.
  • 8 Department of Chemical and Biological Engineering, College of Engineering, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea. [email protected].
  • 9 Natural and Medical Sciences Research Centre, University of Nizwa, P.O. Box 33, PC 616, Birkat Al Mauz, Nizwa, Sultanate of Oman. [email protected].
  • 10 Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Bezmialem Vakif University, Fatih, 34093, Istanbul, Turkey.
  • 11 Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, 60800, Pakistan. [email protected].
PMID: 41290970 DOI: 10.1038/s41598-025-28665-4
Abstract

The most prevalent degenerative brain disease, Alzheimer's disease (AD), is characterized by cognitive function impairment. The ability to code new memories is lost in AD patients, and their lives are very challenging. Inhibitors of cholinesterase (ChE) and Monoamine Oxidase (MAO) have drawn interest as potential therapies for AD. To combat Alzheimer's disease (AD), a new class of Coumarin-hydrazone hybrids has been synthesized 3(a-m). Compounds 3a, 3e, and 3l exhibited significant acetylcholinesterase (AChE) inhibitory activity with low IC50 values of 7.40 ± 0.14 µM, 8.01 ± 0.70 µM, and 8.54 ± 1.01 µM, respectively. Additionally, these compounds, along with 3k, demonstrated potent butyrylcholinesterase (BChE) inhibition, with IC50 values from 65.41 ± 4.55 µM to 74.98 ± 5.30 µM, highlighting their dual cholinesterase inhibitory potential. Compound like 3a (1.44 ± 0.03 µM), 3e (1.51 ± 0.13 µM), and 3l (1.65 ± 0.03 µM) display robust MAO-A inhibition, suggesting high potency. To see how the most potent inhibitor chemicals affected the substrate-enzyme relationship, enzyme kinetic tests were conducted in addition to enzyme inhibition investigations. Compound 3e may function as a dual binding site AChE Inhibitor, according to docking studies in addition to in vitro testing.

Keywords

Anti-Alzheimer; Cholinesterase; Coumarin; DFT; Hydrazones; MAO; Molecular docking; Thiosemicarbazones.

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