Development of an at-line coupling of LC-QTOF-ESI-MS/MS to steroid 5-alpha reductase inhibition assay, a fast bioactive targeting and guided purification of natural complex sample, Impatiens balsamina Linn.

IF 4.5 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic Chemistry Pub Date : 2024-11-16 DOI:10.1016/j.bioorg.2024.107971

Jukkarin Srivilai, Nitra Neungchamnong, Nantaka Khorana, Piyakaset Suksathan, Tammanoon Rungsang, Prapapan Temkittaworn, Ruttanaporn Chantakul, Eakkaluk Wongwad, Ranit Charoenjittichai, Kornkanok Ingkaninan

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引用次数: 0

Abstract

This study provides a rapid and accurate method for screening steroid 5-alpha reductase (S5αR) inhibitors in Impatiens balsamina Linn (IB). using at-line LC-QTOF-ESI-MS/MS coupling S5αR inhibitory assay. IB (Balsaminaceae) is an annual herbaceous plant cultivated in tropical and subtropical regions. It has been used in traditional Chinese and Thai medicine for treatment of hair loss and various skin conditions, potentially through anti-androgenic mechanisms. A combined approach of S5αR inhibitory assay and LC-QTOF-ESI-MS/MS was developed to rapidly screen for target biomarkers and guide their isolation using preparative HPLC. The toxicity of both the extract and isolated biomarkers was evaluated on skin cells, keratinocytes, and fibroblasts. Eight bioactive compounds were identified as two naphthoquinone, two fatty acid derivatives, three nitrogenous compounds and one aromatic derivative. The most potent bioactive markers, identified as 2-methoxy-1,4-naphthoquinone (2MN) and impateinol, were targeted and isolated using preparative HPLC, yielding 5.0 % and 3.5 %, respectively. These compounds exhibited S5αR inhibitory activity higher than that of finasteride drug by 10 and 2 times, respectively. Both the isolated biomarkers and the extract demonstrated a broad therapeutic index. The developed method in this study proved to be both rapid and accurate, making it suitable for screening and targeting S5αR inhibitors in herbal plants or complex matrix samples. It facilitated the fast-guided isolation of bioactive compounds, highlighting its potential for future applications in drug discovery research.

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开发 LC-QTOF-ESI-MS/MS 与类固醇 5-α 还原酶抑制测定的在线耦合、快速生物活性靶向和天然复杂样品 Impatiens balsamina Linn 的引导纯化。

本研究采用在线 LC-QTOF-ESI-MS/MS 联用 S5αR 抑制测定法，为筛选 Impatiens balsamina Linn（IB）中的类固醇 5-α 还原酶（S5αR）抑制剂提供了一种快速准确的方法。香脂树（Balsaminaceae）是一种一年生草本植物，栽培于热带和亚热带地区。在传统的中国和泰国医学中，它被用于治疗脱发和各种皮肤病，这可能是通过抗雄激素机制实现的。研究人员开发了一种结合 S5αR 抑制测定和 LC-QTOF-ESI-MS/MS 的方法，以快速筛选目标生物标记物，并指导使用制备型 HPLC 分离这些标记物。评估了提取物和分离的生物标志物对皮肤细胞、角质细胞和成纤维细胞的毒性。共鉴定出八种生物活性化合物，包括两种萘醌、两种脂肪酸衍生物、三种含氮化合物和一种芳香衍生物。通过制备型高效液相色谱（HPLC）技术，确定了最有效的生物活性标志物，即 2-甲氧基-1,4-萘醌（2MN）和 impateinol，并对其进行了分离，分离率分别为 5.0% 和 3.5%。这些化合物的 S5αR 抑制活性分别是非那雄胺的 10 倍和 2 倍。分离出的生物标记物和提取物都具有广泛的治疗指数。本研究开发的方法既快速又准确，适用于中草药植物或复杂基质样品中S5αR抑制剂的筛选和定位。它有助于快速指导分离生物活性化合物，凸显了其在未来药物发现研究中的应用潜力。

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来源期刊

Bioorganic Chemistry 生物-生化与分子生物学

CiteScore

9.70

自引率

3.90%

发文量

679

审稿时长

31 days

期刊介绍： Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.