Scholarlink

<p>Neurodegenerative disorders and neuroblastoma represent major therapeutic challenges, and multitarget approaches have gained increasing attention. In this study, a series of thiosemicarbazone derivatives (5a–t) was evaluated for their inhibitory activity against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and monoamine oxidase A (MAO-A), together with their cytotoxic effects and molecular interaction profiles. In vitro enzyme assays revealed nanomolar inhibition for several compounds. Notably, compound 5n exhibited potent and balanced multitarget activity with IC<sub>50</sub> values of 104.28 nM (AChE), 23.04 nM (BChE), and 215.50 nM (MAO-A), surpassing galantamine (IC<sub>50</sub> = 296.32 and 105.20 nM for AChE and BChE, respectively) and approaching the activity of clorgyline (IC<sub>50</sub> = 401.68 nM). Kinetic studies confirmed strong enzyme binding, with K<sub>i</sub> values of 92.42 nM (AChE) and 25.35 nM (BChE). Cytotoxicity assays against SH-SY5Y neuroblastoma cells showed selective antiproliferative effects, with compound 5n displaying an IC<sub>50</sub> of 5.23 µM and a selectivity index of 8.6 relative to HUVEC cells. Molecular docking and MM-GBSA analyses revealed strong binding affinities (docking scores − 10.4 to − 15.4&#xa0;kcal/mol; ΔG_bind − 55.9 to − 88.4&#xa0;kcal/mol), which were further supported by molecular dynamics simulations. DFT calculations indicated favorable electronic properties (HOMO–LUMO gap: 0.098–0.116&#xa0;eV), while ADME predictions suggested acceptable drug-like behavior and good oral absorption. These results identify thiosemicarbazone derivative 5n as a promising multitarget lead for the development of agents targeting cholinergic dysfunction, MAO-A inhibition, and neuroblastoma proliferation.</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

Design, synthesis, and multitarget evaluation of thiosemicarbazone–sulfonamide hybrids as potent cholinesterase and MAO-A inhibitors with neuroblastoma-associated cytotoxicity

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月11日

查看全文
  • Khawar Abbas,
  • Mohamed Rahmtalla Elamin,
  • Halil Şenol,
  • Furkan Çakır,
  • Parham Taslimi,
  • Feyzi Sinan Tokali,
  • Nadeem Raza,
  • Mostafa E. Salem,
  • Rima D. Alharthy,
  • Asif Rasool,
  • Zahid Shafiq

摘要

Neurodegenerative disorders and neuroblastoma represent major therapeutic challenges, and multitarget approaches have gained increasing attention. In this study, a series of thiosemicarbazone derivatives (5a–t) was evaluated for their inhibitory activity against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and monoamine oxidase A (MAO-A), together with their cytotoxic effects and molecular interaction profiles. In vitro enzyme assays revealed nanomolar inhibition for several compounds. Notably, compound 5n exhibited potent and balanced multitarget activity with IC50 values of 104.28 nM (AChE), 23.04 nM (BChE), and 215.50 nM (MAO-A), surpassing galantamine (IC50 = 296.32 and 105.20 nM for AChE and BChE, respectively) and approaching the activity of clorgyline (IC50 = 401.68 nM). Kinetic studies confirmed strong enzyme binding, with Ki values of 92.42 nM (AChE) and 25.35 nM (BChE). Cytotoxicity assays against SH-SY5Y neuroblastoma cells showed selective antiproliferative effects, with compound 5n displaying an IC50 of 5.23 µM and a selectivity index of 8.6 relative to HUVEC cells. Molecular docking and MM-GBSA analyses revealed strong binding affinities (docking scores − 10.4 to − 15.4 kcal/mol; ΔG_bind − 55.9 to − 88.4 kcal/mol), which were further supported by molecular dynamics simulations. DFT calculations indicated favorable electronic properties (HOMO–LUMO gap: 0.098–0.116 eV), while ADME predictions suggested acceptable drug-like behavior and good oral absorption. These results identify thiosemicarbazone derivative 5n as a promising multitarget lead for the development of agents targeting cholinergic dysfunction, MAO-A inhibition, and neuroblastoma proliferation.