丁香宁对细胞色素 P450 3A4 和 2D6 的相互作用研究：多光谱法和分子对接。
Interaction study of engeletin toward cytochrome P450 3A4 and 2D6 by multi-spectroscopy and molecular docking.
机构信息
The College of Chemistry, Changchun Normal University, Changchun 130032,China.
The College of Chemistry, Changchun Normal University, Changchun 130032,China.
出版信息
Spectrochim Acta A Mol Biomol Spectrosc. 2022 Jan 5;264:120311. doi: 10.1016/j.saa.2021.120311. Epub 2021 Aug 26.
The inhibitory effects of engeletin on the activities of human cytochrome P450 3A4 and 2D6 (CYP3A4 and CYP2D6) were investigated by enzyme kinetics, multi-spectroscopy and molecular docking. Engeletin was found to strongly inhibit CYP3A4 and CYP2D6, with the IC of 1.32 μM and 2.87 μM, respectively. The inhibition modes of engeletin against CYP3A4 and CYP2D6 were a competitive type and a mixed type, respectively. The fluorescence of the two CYPs was quenched statically by engeletin, which was bound to CYP3A4 stronger than to CYP2D6 at the same temperature. Circular dichroism spectroscopy, three-dimensional fluorescence, ultraviolet-visible spectroscopy and synchronous fluorescence confirmed that the conformation and micro-environment of the two CYPs protein were changed after binding with engeletin. Molecular docking, ultraviolet-visible spectroscopy and the fluorescence data revealed that engeletin had strong binding affinity to the two CYPs through hydrogen and van der Waals forces. The findings here suggested that engeletin may cause the herb-drug interactions for its inhibition of CYP3A4 and CYP2D6 activities.
通过酶动力学、多光谱和分子对接研究了栀子苷对人细胞色素 P450 3A4 和 2D6（CYP3A4 和 CYP2D6）活性的抑制作用。发现栀子苷强烈抑制 CYP3A4 和 CYP2D6，其 IC 分别为 1.32 μM 和 2.87 μM。栀子苷对 CYP3A4 和 CYP2D6 的抑制模式分别为竞争性和混合型。栀子苷静态猝灭了两种 CYP 的荧光，在相同温度下，栀子苷与 CYP3A4 的结合比与 CYP2D6 更强。圆二色性光谱、三维荧光、紫外可见光谱和同步荧光证实，栀子苷与 CYP3A4 和 CYP2D6 结合后，两种 CYP 蛋白的构象和微环境发生了变化。分子对接、紫外可见光谱和荧光数据表明，栀子苷通过氢键和范德华力与两种 CYP 具有很强的结合亲和力。这些发现表明，栀子苷可能因其抑制 CYP3A4 和 CYP2D6 活性而导致草药-药物相互作用。
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