Maria Miguel Coelho, Rita Lima, Ana Sofia Almeida, Pedro Alexandrino Fernandes, Fernando Remião, Carla Fernandes, Maria Elizabeth Tiritan
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PMZ and its metabolites exhibited a notable binding affinity for HSA (%b values higher than 80%), while COD exhibited a %b value of 65%. To discern the specific sites of HSA to which these compounds were bound, displacement experiments were performed using warfarin and (S)-ibuprofen as probes for sites I and II, respectively, which revealed that all analytes were bound to both sites. Molecular docking studies corroborated the experimental results, reinforcing the insights gained from the empirical data. The in silico data also suggested that competition between PMZ and its metabolites with COD can occur in both sites of HSA, but mainly in site II. 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引用次数: 0
摘要
"紫色饮料 "是一种含有异丙嗪(PMZ)和可待因(COD)的软饮料,因其致幻效果而风靡全球。大量饮用这种混合饮料可能会导致致命的后果。这些药物与血浆蛋白的结合会增加药物相互作用、副作用和/或毒性的风险,从而使问题更加严重。本文采用分区方法,通过高效亲和层析(HPAC)研究了PMZ及其主要代谢物[N-去甲基异丙嗪(DMPMZ)和异丙嗪亚砜(PMZSO)]以及COD与人血清白蛋白(HSA)的结合亲和力。PMZ及其代谢物对HSA具有显著的结合亲和力(%b值高于80%),而COD的%b值为65%。为了确定这些化合物与 HSA 结合的特定位点,分别用华法林和 (S)- 布洛芬作为位点 I 和位点 II 的探针进行了位移实验,结果表明所有分析物都与这两个位点结合。分子对接研究证实了实验结果,加强了从经验数据中获得的启示。硅学数据还表明,PMZ 及其代谢物与 COD 之间的竞争可能发生在 HSA 的两个位点,但主要发生在位点 II。由于目标化合物是手性的,因此还探讨了与 HSA 结合的对映体选择性,结果表明这些化合物的结合没有对映体选择性。
Binding studies of promethazine and its metabolites with human serum albumin by high-performance affinity chromatography and molecular docking in the presence of codeine.
"Purple Drank", a soft drink containing promethazine (PMZ) and codeine (COD), has gained global popularity for its hallucinogenic effects. Consuming large amounts of this combination can lead to potentially fatal events. The binding of these drugs to plasma proteins can exacerbate the issue by increasing the risk of drug interactions, side effects, and/or toxicity. Herein, the binding affinity to human serum albumin (HSA) of PMZ and its primary metabolites [N-desmethyl promethazine (DMPMZ) and promethazine sulphoxide (PMZSO)], along with COD, was investigated by high-performance affinity chromatography (HPAC) though zonal approach. PMZ and its metabolites exhibited a notable binding affinity for HSA (%b values higher than 80%), while COD exhibited a %b value of 65%. To discern the specific sites of HSA to which these compounds were bound, displacement experiments were performed using warfarin and (S)-ibuprofen as probes for sites I and II, respectively, which revealed that all analytes were bound to both sites. Molecular docking studies corroborated the experimental results, reinforcing the insights gained from the empirical data. The in silico data also suggested that competition between PMZ and its metabolites with COD can occur in both sites of HSA, but mainly in site II. As the target compounds are chiral, the enantioselectivity for HSA binding was also explored, showing that the binding for these compounds was not enantioselective.
期刊介绍:
Analytical and Bioanalytical Chemistry’s mission is the rapid publication of excellent and high-impact research articles on fundamental and applied topics of analytical and bioanalytical measurement science. Its scope is broad, and ranges from novel measurement platforms and their characterization to multidisciplinary approaches that effectively address important scientific problems. The Editors encourage submissions presenting innovative analytical research in concept, instrumentation, methods, and/or applications, including: mass spectrometry, spectroscopy, and electroanalysis; advanced separations; analytical strategies in “-omics” and imaging, bioanalysis, and sampling; miniaturized devices, medical diagnostics, sensors; analytical characterization of nano- and biomaterials; chemometrics and advanced data analysis.