Synthesis, Antioxidant Activity, and Molecular Docking of Novel Paeoniflorin Derivatives

IF 3.2 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Jiating Ni, Meng Yang, Xinyue Zheng, Mingtao Wang, Qian Xiao, Hua Han, Peiliang Dong
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Abstract

Paeoniflorin (PF) is one of the active constituents of the traditional Chinese medicine Paeoniae Radix Rubra and has been actively explored in the pharmaceutical area due to its numerous pharmacological effects. However, severe difficulties such as limited bioavailability and low permeability limit its utilization. Therefore, this study developed and synthesized 25 derivatives of PF, characterized them by 1H NMR, 13C NMR, and HR-MS, and evaluated their antioxidant activity. Firstly, the antioxidant capacity of PF derivatives was investigated through DPPH radical scavenging experiment, ABTS radical scavenging experiment, reducing ability experiment, and O2.− radical scavenging experiment. PC12 cells are routinely used to evaluate the antioxidant activity of medicines, therefore we utilize it to establish a cellular model of oxidative stress. Among all derivatives, compound 22 demonstrates high DPPH radical scavenging capacity, ABTS radical scavenging ability, reduction ability, and O2.− radical scavenging ability. The results of cell tests reveal that compound 22 has a non-toxic effect on PC12 cells and a protective effect on H2O2-induced oxidative stress models. This might be due to the introduction of 2, 5-difluorobenzene sulfonate group in PF, which helps in scavenging free radicals under oxidative stress. Western blot and molecular docking indicated that compound 22 may exert antioxidant activity by activating Nrf2 protein expression. As noted in the study, compound 22 has the potential to be a novel antioxidant.

新型芍药苷衍生物的合成、抗氧化活性和分子对接
芍药苷(PF)是传统中药芍药的活性成分之一,因其药理作用众多而在制药领域被积极探索。然而,生物利用度有限和渗透性低等严重困难限制了其应用。因此,本研究开发并合成了 25 种 PF 衍生物,通过 1H NMR、13C NMR 和 HR-MS 对其进行了表征,并评估了它们的抗氧化活性。首先,通过 DPPH 自由基清除实验、ABTS 自由基清除实验、还原能力实验和 O2 自由基清除实验研究了 PF 衍生物的抗氧化能力。PC12 细胞是评估药物抗氧化活性的常规细胞,因此我们利用它来建立氧化应激的细胞模型。在所有衍生物中,化合物 22 具有较高的 DPPH 自由基清除能力、ABTS 自由基清除能力、还原能力和 O2.- 自由基清除能力。细胞测试结果表明,化合物 22 对 PC12 细胞无毒,对 H2O2 诱导的氧化应激模型有保护作用。这可能是由于 PF 中引入了 2,5-二氟苯磺酸基团,有助于清除氧化应激下的自由基。Western 印迹和分子对接表明,化合物 22 可通过激活 Nrf2 蛋白表达来发挥抗氧化活性。正如研究中所指出的,化合物 22 有可能成为一种新型抗氧化剂。
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来源期刊
Chemical Biology & Drug Design
Chemical Biology & Drug Design 医学-生化与分子生物学
CiteScore
5.10
自引率
3.30%
发文量
164
审稿时长
4.4 months
期刊介绍: Chemical Biology & Drug Design is a peer-reviewed scientific journal that is dedicated to the advancement of innovative science, technology and medicine with a focus on the multidisciplinary fields of chemical biology and drug design. It is the aim of Chemical Biology & Drug Design to capture significant research and drug discovery that highlights new concepts, insight and new findings within the scope of chemical biology and drug design.
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