Structural Biology Unit, Integrative Neuroscience Branch, NIDA IRP, NIH, Baltimore, MD, USA.
Ionwerks Inc., Houston, TX, USA.
J Am Soc Mass Spectrom. 2019 Jul;30(7):1199-1203. doi: 10.1007/s13361-019-02166-x. Epub 2019 Apr 4.
In this paper, drug-drug chemical interactions between two different aromatic compounds were studied by mass spectrometry. Specifically, we examined non-covalent complexes (NCX) between paclitaxel, a chemotherapeutic compound, and medications widely used in palliative care for depression, psychosis, and anxiety. It is unknown whether psychotropic medications directly interact with paclitaxel. Here, we use a simple and rapid electrospray ionization mass spectrometry in vitro assay, which has been predictive in the case of neuropeptides, to measure the relative strength of non-covalent interactions. This chemical interaction is most likely due to the overlap of aromatic rings of π-orbitals between paclitaxel and five commonly used medications: diazepam, clonozepam, sertraline, fluoxetine, and haloperidol. Molecular modeling illustrates that differences in the stability of the NCXs are likely due to the distance between the aromatic rings present in both the paclitaxel and antidepressant medications. Graphical Abstract.
本文通过质谱法研究了两种不同芳香族化合物之间的药物-药物化学相互作用。具体来说，我们研究了紫杉醇（一种化疗药物）与广泛用于姑息治疗抑郁症、精神病和焦虑症的药物之间的非共价复合物（NCX）。目前尚不清楚精神药物是否会直接与紫杉醇相互作用。在这里，我们使用一种简单快速的电喷雾电离质谱体外测定法，该方法在神经肽的情况下具有预测性，以测量非共价相互作用的相对强度。这种化学相互作用很可能是由于紫杉醇和五种常用药物（地西泮、氯硝西泮、舍曲林、氟西汀和氟哌啶醇）之间的π 轨道芳香环重叠所致。分子建模表明，NCX 的稳定性差异可能是由于紫杉醇和抗抑郁药物中存在的芳香环之间的距离不同所致。图表摘要。
