School of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi 530004, China; China Academy of Science and Technology Development Guangxi Branch, Nanning, Guangxi 530022, China.
College of Animal Science and Technology, Guangxi University, Nanning, Guangxi 530005, China.
Life Sci. 2020 Apr 15;247:117439. doi: 10.1016/j.lfs.2020.117439. Epub 2020 Feb 16.
This study was aimed to synthesize novel caffeic acid derivatives and evaluate their potential applications for the treatment of oxidative stress associated disease.
Caffeic acid sulfonamide derivatives were synthesized by coupling sulfonamides to the backbone of caffeic acid and fully characterized by melting point test, FT-IR, MS, NMR, UV-vis and n-octanol-water distribution assay. Their free radical scavenging ability was evaluated using DPPH assay and cytotoxicity against A549 cells were determined by MTT assay. The protective effect of these derivatives against hydrogen peroxide (HO) induced oxidative injury was assessed in A549 cells from cell viability, production of reactive oxygen species (ROS) and malondialdehyde (MDA), alternation of antioxidase activities, and expressions of Nrf2 and its target genes.
Six novel caffeic acid sulfonamide derivatives were obtained. The derivatives showed better liphophilicity than the parent caffeic acid. CASMZ, CAST and CASQ exhibited similar DPPH scavenging capability as caffeic acid, while the protection of hydroxyl groups on the benzene ring with acetyl groups caused decrease in radical scavenging activity. No inhibitory effect on the proliferation of A549 cells were observed up to a concentration of 50 μM. Pre-treatment of cells with these derivatives strongly inhibited HO induced decrease of cell viability, reduced the production of ROS and MDA, promoted antioxidase activities, and further upregulated the expression of Nrf2 and its target genes.
Caffeic acid sulfonamide derivatives were synthesized with simple reactions under mild conditions. They might protect cells from HO-induced oxidative injury via Nrf2 pathway.
本研究旨在合成新型咖啡酸衍生物，并评估其在治疗与氧化应激相关疾病方面的潜在应用。
通过将磺酰胺偶联到咖啡酸的主链上，合成了咖啡酸磺酰胺衍生物，并通过熔点测试、FT-IR、MS、NMR、UV-vis 和正辛醇-水分配测定法对其进行了全面表征。通过 DPPH 测定法评估了它们的自由基清除能力，并用 MTT 测定法测定了它们对 A549 细胞的细胞毒性。通过测定细胞活力、活性氧（ROS）和丙二醛（MDA）的产生、抗氧化酶活性的改变以及 Nrf2 及其靶基因的表达，评估了这些衍生物对过氧化氢（HO）诱导的氧化损伤的保护作用。
获得了 6 种新型咖啡酸磺酰胺衍生物。与母体咖啡酸相比，这些衍生物具有更好的亲脂性。CASMZ、CAST 和 CASQ 表现出与咖啡酸相似的 DPPH 清除能力，而苯环上的羟基被乙酰基取代会导致自由基清除活性下降。在 50 μM 浓度下，这些衍生物对 A549 细胞的增殖没有抑制作用。用这些衍生物预处理细胞可强烈抑制 HO 诱导的细胞活力下降，减少 ROS 和 MDA 的产生，促进抗氧化酶活性，并进一步上调 Nrf2 及其靶基因的表达。
通过简单的反应在温和条件下合成了咖啡酸磺酰胺衍生物。它们可能通过 Nrf2 途径保护细胞免受 HO 诱导的氧化损伤。
