Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Synthesis, Biological Evaluation and Molecular Modeling Studies of Methyl Indole-Isoxazole Carbohydrazide Derivatives As Multi-Target Anti-Alzheimer’S Agents Publisher Pubmed



Iraji A1, 2 ; Nikfar P3 ; Nazari Montazer M4 ; Karimi M5 ; Edraki N6 ; Saeedi M7, 8 ; Mirfazli SS3
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Persian Medicine, School of Medicine, Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
  2. 2. Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  3. 3. Department of Medicinal Chemistry, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran
  4. 4. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Chemistry, North Tehran Branch, Islamic Azad University, Tehran, Iran
  6. 6. Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  7. 7. Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  8. 8. Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran

Source: Scientific Reports Published:2024


Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that affects the elderly population globally and there is an urgent demand for developing novel anti-AD agents. In this study, a new series of indole-isoxazole carbohydrazides were designed and synthesized. The structure of all compounds was elucidated using spectroscopic methods including FTIR, 1H NMR, and 13C NMR as well as mass spectrometry and elemental analysis. All derivatives were screened for their acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity. Out of all synthesized compounds, compound 5d exhibited the highest potency as AChE inhibitor with an IC50 value of 29.46 ± 0.31 µM. It showed significant selectivity towards AChE, with no notable inhibition against BuChE. A kinetic study on AChE for compound 5d indicated a competitive inhibition pattern. Also, 5d exhibited promising BACE1 inhibitory potential with an IC50 value of 2.85 ± 0.09 µM and in vitro metal chelating ability against Fe3+. The molecular dynamic studies of 5d against both AChE and BACE1 were executed to evaluate the behavior of this derivative in the binding site. The results showed that the new compounds deserve further chemical optimization to be considered potential anti-AD agents. © The Author(s) 2024.
Related Docs
View other Related Docs
1. Synthesis and Evaluation of Novel Arylisoxazoles Linked to Tacrine Moiety: In Vitro and in Vivo Biological Activities Against Alzheimer’S Disease, Molecular Diversity (2022)
2. Synthesis and Bio-Evaluation of New Multifunctional Methylindolinone-1,2,3-Triazole Hybrids As Anti-Alzheimer's Agents, Journal of Molecular Structure (2021)
3. Synthesis and Biological Activity of Some Benzochromenoquinolinones: Tacrine Analogs As Potent Anti-Alzheimer's Agents, Chemistry and Biodiversity (2019)
4. Design and Synthesis of Multi-Target Directed 1,2,3-Triazole-Dimethylaminoacryloyl-Chromenone Derivatives With Potential Use in Alzheimer's Disease, BMC Chemistry (2020)
5. Isoindolinedione-Benzamide Pyridinium Derivatives for Targeting Alzheimer’S Disease, ACS Omega (2024)
6. Synthesis and in Vitro Biological Activity Evaluation of Novel Imidazo [2,1-B][1,3,4] Thiadiazole As Anti-Alzheimer Agents, Letters in Drug Design and Discovery (2020)
7. Design and Synthesis of Novel Arylisoxazole-Chromenone Carboxamides: Investigation of Biological Activities Associated With Alzheimer's Disease, Chemistry and Biodiversity (2020)
8. Phenyl-Quinoline Derivatives As Lead Structure of Cholinesterase Inhibitors With Potency to Reduce the Gsk-3Β Level Targeting Alzheimer's Disease, International Journal of Biological Macromolecules (2023)
Experts (# of related papers)
View all Related Experts
Mohammad Mahdavi (10)
Mina Saeedi (8)
Other Related Docs
9. Cyanoacetohydrazide Linked to 1,2,3-Triazole Derivatives: A New Class of Α-Glucosidase Inhibitors, Scientific Reports (2022)
10. Novel N-Benzylpyridinium Moiety Linked to Arylisoxazole Derivatives As Selective Butyrylcholinesterase Inhibitors: Synthesis, Biological Evaluation, and Docking Study, Bioorganic Chemistry (2019)
11. Synthesis and Tyrosinase Inhibitory Activities of Novel Isopropylquinazolinones, BMC Chemistry (2023)
12. Design and Synthesis of Selective Acetylcholinesterase Inhibitors: Arylisoxazole-Phenylpiperazine Derivatives, Chemistry and Biodiversity (2019)
13. Amino-7,8-Dihydro-4H-Chromenone Derivatives As Potential Inhibitors of Acetylcholinesterase and Butyrylcholinesterase for Alzheimer’S Disease Management; in Vitro and in Silico Study, BMC Chemistry (2024)