Determination of 3- and 4-chloromethcathinone interactions with plasma proteins: study involving analytical and theoretical methods

IF 2.8 4区 医学 Q2 TOXICOLOGY
Piotr Holowinski, Michal P. Dybowski
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引用次数: 0

Abstract

Purpose

The purpose of this paper was to determine 3- and 4-chloromethcathinone (3- and 4-CMC) binding degree and possible binding interaction modes with human serum albumin (HSA) using analytical and theoretical methods.

Methods

Experimental determination of 3- and 4-CMC binding degree with HSA was performed using gas chromatography–tandem mass spectrometry preceded by the equilibrium dialysis (ED) and ultrafiltration (UF). Nuclear magnetic resonance (NMR) spectroscopy was used to determine 3- and 4-CMC epitope-binding maps and possible binding sites in HSA. The molecular docking and molecular dynamics were employed to obtain detailed information about binding modes of 3- and 4-CMC enantiomers in HSA.

Results

As follows from the presented data, the degree of binding of 3- and 4-CMC is at a similar level of approx. 80%. This indicates a relatively strong binding of CMC to plasma proteins. The model studies employing the NMR spectroscopy and molecular simulations indicate that both CMCs bind to HSA. The whole 3- and 4-CMC molecules are embedded in the binding sites, with aromatic moieties being in the closest contact with the HSA residues. Moreover, conducted experiments show that Sudlow site II is the main binding center for 3- and 4-CMC and Sudlow site I acts as the secondary binding site.

Conclusions

Although many studies describe pharmacological and toxicological properties of synthetic cathinones (SC), the data taking SCs binding in plasma into consideration are scarce. To our knowledge, this is the first report presenting comprehensive experimental and theoretical characterization of 3- and 4-CMC binding with plasma proteins.

Abstract Image

测定 3-和 4-氯甲卡西酮与血浆蛋白的相互作用:涉及分析和理论方法的研究
方法在平衡透析(ED)和超滤(UF)之前,采用气相色谱-串联质谱法实验测定 3-和 4-氯甲卡西酮(3-和 4-CMC)与人血清白蛋白(HSA)的结合程度和可能的结合相互作用模式。核磁共振(NMR)光谱用于确定 3-CMC 和 4-CMC 表位结合图和 HSA 中可能的结合位点。通过分子对接和分子动力学研究,获得了 3-CMC 和 4-CMC 对映异构体在 HSA 中结合模式的详细信息。这表明 CMC 与血浆蛋白的结合力相对较强。利用核磁共振光谱和分子模拟进行的模型研究表明,两种 CMC 都能与 HSA 结合。整个 3-CMC 和 4-CMC 分子都嵌入了结合位点,其中芳香分子与 HSA 残基的接触最为密切。此外,实验还表明,Sudlow 位点 II 是 3-CMC 和 4-CMC 的主要结合中心,而 Sudlow 位点 I 则是次要结合位点。据我们所知,这是第一份全面介绍 3-CMC 和 4-CMC 与血浆蛋白结合的实验和理论特征的报告。
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来源期刊
Forensic Toxicology
Forensic Toxicology TOXICOLOGY-
CiteScore
5.80
自引率
9.10%
发文量
40
审稿时长
3 months
期刊介绍: The journal Forensic Toxicology provides an international forum for publication of studies on toxic substances, drugs of abuse, doping agents, chemical warfare agents, and their metabolisms and analyses, which are related to laws and ethics. It includes original articles, reviews, mini-reviews, short communications, and case reports. Although a major focus of the journal is on the development or improvement of analytical methods for the above-mentioned chemicals in human matrices, appropriate studies with animal experiments are also published. Forensic Toxicology is the official publication of the Japanese Association of Forensic Toxicology (JAFT) and is the continuation of the Japanese Journal of Forensic Toxicology (ISSN 0915-9606).
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