Faculty of Chemistry, Department of Chromatography, Institute of Chemical Sciences, Maria Curie Sklodowska University in Lublin, 20-031, Lublin, Poland.
Forensic Toxicol. 2024 Jul;42(2):111-124. doi: 10.1007/s11419-023-00677-7. Epub 2023 Dec 18.
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.
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.
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.
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.
本文旨在通过分析和理论方法，确定 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。
使用气相色谱-串联质谱法（GC-MS/MS）结合平衡透析（ED）和超滤（UF）实验测定 3- 和 4-CMC 与 HSA 的结合程度。使用核磁共振（NMR）光谱测定 3- 和 4-CMC 表位结合图谱和 HSA 中可能的结合位点。采用分子对接和分子动力学方法，获得 3- 和 4-CMC 对映体在 HSA 中结合模式的详细信息。
从呈现的数据可以看出，3- 和 4-CMC 的结合程度大致相同，约为 80%。这表明 CMC 与血浆蛋白的结合相对较强。采用 NMR 光谱和分子模拟的模型研究表明，两种 CMC 都与 HSA 结合。整个 3- 和 4-CMC 分子都嵌入在结合位点中，芳香部分与 HSA 残基最接近。此外，进行的实验表明，Sudlow 位点 II 是 3- 和 4-CMC 的主要结合中心，而 Sudlow 位点 I 则作为次要结合点。
尽管许多研究描述了合成卡西酮（SC）的药理学和毒理学特性，但考虑到 SC 在血浆中的结合数据却很少。据我们所知，这是首次全面描述 3- 和 4-CMC 与血浆蛋白结合的实验和理论特征的报告。
