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2-羟基-3-(4-芳基-1-哌嗪基)丙基邻苯二甲酰亚胺衍生物作为前药-与血浆蛋白的光谱和理论结合研究。

The 2-hydroxy-3-(4-aryl-1-piperazinyl)propyl Phthalimide Derivatives as Prodrugs-Spectroscopic and Theoretical Binding Studies with Plasma Proteins.

机构信息

Department of Inorganic Chemistry, Wroclaw Medical University, ul. Borowska 211a, 50-556 Wrocław, Poland.

Department of Medicinal Chemistry, Wroclaw Medical University, ul. Borowska 211, 50-556 Wroclaw, Poland.

出版信息

Int J Mol Sci. 2022 Jun 23;23(13):7003. doi: 10.3390/ijms23137003.

Abstract

Many publications in databases deal with the interactions of new drugs with albumin. However, it is not only albumin that is responsible for binding pharmaceutical molecules to proteins in the human body. There are many more proteins in plasma that are important for the study of the ADME pathway. Therefore, in this study, we have shown the results of the interactions between the plasma proteins albumin, orosomucoid, and gamma globulins and non-toxic anti-inflammatory phthalimide analogs, which due to the promising obtained results, may be potential candidates in the group of analgesic and anti-inflammatory drugs. Using spectroscopic methods and molecular modeling, we showed that all four tested compounds form complexes with the analyzed proteins. The formation of a complex with proteins raises the pharmacological efficacy of the drug. Therefore, the obtained results could be a step in the study of the pharmacokinetics and pharmacodynamics of new potential pharmaceuticals.

摘要

许多数据库中的出版物都涉及新药与白蛋白的相互作用。然而,负责将药物分子与人体内蛋白质结合的不仅仅是白蛋白。在血浆中还有许多其他蛋白质对于 ADME 途径的研究很重要。因此,在这项研究中,我们展示了血浆蛋白白蛋白、乳白蛋白和γ球蛋白与非毒性抗炎邻苯二甲酰亚胺类似物之间相互作用的结果,由于得到了有希望的结果,这些类似物可能成为镇痛和抗炎药物组中的潜在候选药物。使用光谱方法和分子建模,我们表明所有四种测试化合物都与分析的蛋白质形成复合物。与蛋白质形成复合物会提高药物的药理功效。因此,所获得的结果可能是研究新的潜在药物药代动力学和药效学的一个步骤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e76/9266550/753b97c7f4e7/ijms-23-07003-g001.jpg

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