Scholarlink

<p>Dopamine is an essential neurotransmitter found in both vertebrates and invertebrates which regulates motor coordination, cognition, emotional processing, and autonomic functions. Dopamine is biosynthesized from L-tyrosine and is primarily metabolized by catechol-O-methyltransferase (COMT), which regulates its concentration and ensures proper synaptic signalling within the basal ganglia. Dopamine deficiency, the hallmark of Parkinson’s disease, is a progressive neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra pars compacta. To alleviate dopamine deficiency, current therapeutic strategies include administration of the dopamine precursor levodopa in combination with COMT inhibitors, which enhance levodopa bioavailability and prolong its therapeutic effect. However, the clinical utility of synthetic COMT inhibitors is often limited by hepatotoxicity and other adverse effects, underscoring the need for safer alternatives. In this context, plant-derived bioactive compounds are being increasingly investigated as potential inhibitors of COMT activity. Our study evaluated the affinity of 170 phytochemicals from <i>Tamarindus indica</i> against COMT utilizing computational strategies. Gallacetophenone, an aromatic ketone, was identified as a promising candidate that met the requirements for drug-likeness. Molecular dynamics (MD) simulations, supported by post-MDS analyses, principal component analysis, and free energy landscape analyses, demonstrated that gallacetophenone binding enhances the conformational stability of 3BWY compared to the control. These findings suggest that gallacetophenone may serve as a potential therapeutic phytochemical; however, its efficacy remains computationally predicted and requires validation through targeted in vitro and in vivo studies.</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

Evaluation of phytochemicals from Tamarindus indica as a potential catechol-O-methyltransferase (COMT) inhibitor: an in-silico approach for Parkinson’s disease

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月19日

查看全文
  • Aparna G. Shenoy,
  • Ashin John,
  • Vishal Ravi,
  • Kiyan Kapur,
  • Gowtham Nirmal Jonnalagadda,
  • Rajesh Raju,
  • Mohammad Raish,
  • Niyas Rehman

摘要

Dopamine is an essential neurotransmitter found in both vertebrates and invertebrates which regulates motor coordination, cognition, emotional processing, and autonomic functions. Dopamine is biosynthesized from L-tyrosine and is primarily metabolized by catechol-O-methyltransferase (COMT), which regulates its concentration and ensures proper synaptic signalling within the basal ganglia. Dopamine deficiency, the hallmark of Parkinson’s disease, is a progressive neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra pars compacta. To alleviate dopamine deficiency, current therapeutic strategies include administration of the dopamine precursor levodopa in combination with COMT inhibitors, which enhance levodopa bioavailability and prolong its therapeutic effect. However, the clinical utility of synthetic COMT inhibitors is often limited by hepatotoxicity and other adverse effects, underscoring the need for safer alternatives. In this context, plant-derived bioactive compounds are being increasingly investigated as potential inhibitors of COMT activity. Our study evaluated the affinity of 170 phytochemicals from Tamarindus indica against COMT utilizing computational strategies. Gallacetophenone, an aromatic ketone, was identified as a promising candidate that met the requirements for drug-likeness. Molecular dynamics (MD) simulations, supported by post-MDS analyses, principal component analysis, and free energy landscape analyses, demonstrated that gallacetophenone binding enhances the conformational stability of 3BWY compared to the control. These findings suggest that gallacetophenone may serve as a potential therapeutic phytochemical; however, its efficacy remains computationally predicted and requires validation through targeted in vitro and in vivo studies.