Scholarlink

Background <p>Increasingly, people are turning to using medicinal plants to block particular enzymes in the body to treat various illnesses. Finding additional naturally occurring plant-based chemicals with enzyme-inhibitory qualities is therefore becoming more and more important, especially as they might have fewer side effects than some of the synthetic drugs that are now on the market.</p> Results <p>Semi-synthesis was used to produce two derivatized diacetylated products, cleomiscosin C diacetate (2&#xa0;A) and cleomiscosin A diacetate (1&#xa0;A), from the previously identified cleomiscosins A and C from Allophylus spicatus. In vitro and in silico investigations assessed the compounds’ anti-butyrylcholinesterase (BChE) capability. Compounds 1&#xa0;A and 2&#xa0;A demonstrated significant inhibition of butyrylcholinesterase (BChE), suggesting that they may have anti-BChE properties. Their anti-butyrylcholinesterase activity (IC50 values) to the standard, Eserine (9.3 ± 0.15), ranges from 40.1 ± 0.11 to 55.4 ± 0.17 µM. It was found that 1&#xa0;A and 2&#xa0;A may bind to the hydrophobic gorge of human butyrylcholinesterase (hBChE) similarly to decamethonium using molecular dynamic modeling investigations. These compounds interacted with residues, particularly the P-sites Tyr332 and the A-sites Trp82, Trp231, and Phe329, that are crucial for inhibiting the hBChE enzyme. The RMSD plots and mean values of complexes relative to the unbound proteins show that the binding of 1&#xa0;A and 2&#xa0;A to the enzyme’s binding site did not alter the structural integrity of the protein.</p> Conclusion <p>The findings of this investigation imply that these substances may find application in the treatment of Alzheimer’s disease as butyrylcholinesterase inhibitors.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Derivatization and Anti-Butyrylcholinesterase Activity of Coumarinolignans: Experimental and Computational Approaches

  • 期刊论文

  • 发表日期：

    2025年2月10日

查看全文
  • Ejike Onwudiegwu Okpala,
  • Oloruntoba Emmanuel Yeye,
  • Akingbolabo Daniel Ogunlakin,
  • Godfrey Okechukwu Eneogwe,
  • Gideon Ampoma Gyebi,
  • Oluwafemi Adeleke Ojo,
  • Oluwakayode Olubunmi Odeja,
  • Michael Gabriel Ibok,
  • Clement Odunayo Ajiboye,
  • Patricia Akpomedaye Onocha,
  • Mehreen Lateef,
  • Muhammad Shaiq Ali

摘要

Background

Increasingly, people are turning to using medicinal plants to block particular enzymes in the body to treat various illnesses. Finding additional naturally occurring plant-based chemicals with enzyme-inhibitory qualities is therefore becoming more and more important, especially as they might have fewer side effects than some of the synthetic drugs that are now on the market.

Results

Semi-synthesis was used to produce two derivatized diacetylated products, cleomiscosin C diacetate (2 A) and cleomiscosin A diacetate (1 A), from the previously identified cleomiscosins A and C from Allophylus spicatus. In vitro and in silico investigations assessed the compounds’ anti-butyrylcholinesterase (BChE) capability. Compounds 1 A and 2 A demonstrated significant inhibition of butyrylcholinesterase (BChE), suggesting that they may have anti-BChE properties. Their anti-butyrylcholinesterase activity (IC50 values) to the standard, Eserine (9.3 ± 0.15), ranges from 40.1 ± 0.11 to 55.4 ± 0.17 µM. It was found that 1 A and 2 A may bind to the hydrophobic gorge of human butyrylcholinesterase (hBChE) similarly to decamethonium using molecular dynamic modeling investigations. These compounds interacted with residues, particularly the P-sites Tyr332 and the A-sites Trp82, Trp231, and Phe329, that are crucial for inhibiting the hBChE enzyme. The RMSD plots and mean values of complexes relative to the unbound proteins show that the binding of 1 A and 2 A to the enzyme’s binding site did not alter the structural integrity of the protein.

Conclusion

The findings of this investigation imply that these substances may find application in the treatment of Alzheimer’s disease as butyrylcholinesterase inhibitors.