Institute for Information Technologies, Department of Science, University of Kragujevac, Kragujevac, Serbia.
Department of Natural Science and Mathematics, State University of Novi Pazar, Novi Pazar, Serbia.
Free Radic Res. 2024 Aug-Sep;58(8-9):493-508. doi: 10.1080/10715762.2024.2400674. Epub 2024 Sep 12.
This study examined the antiradical activity of three synthesized coumarin derivatives: ()-3-(1-((2-hydroxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl acetate (), ()-3-(1-((3-hydroxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl acetate (), and ()-3-(1-((4-hydroxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl acetate () against HOO•/O2•- radical species. The investigation included electron spin resonance (ESR) measurements and a DFT kinetic study. Thermodynamic and kinetic parameters of antiradical mechanisms-Formal Hydrogen Atom Transfer (-HAT), Radical Adduct Formation (RAF), Sequential Proton Loss followed by Electron Transfer (SPLET), and Single-Electron Transfer followed by Proton Transfer (SET-PT)-were evaluated using the Quantum Mechanics-based test for Overall Free Radical Scavenging Activity (QM-ORSA) under physiological conditions. ESR results indicated antiradical activity decreased in the sequence (58.7%) > (57.5%) > (53.1%). Kinetic analysis revealed the -HAT mechanism dominated HOO inactivation. A newly formulated Sequential Proton Loss followed by Radical Adduct Formation (SPL-RAF) mechanism described interactions with O. The activity toward O was (1.26 × 10 Ms) > (7.71 × 10 Ms) > (4.22 × 10 Ms). Molecular docking and dynamics studies tested inhibitory capability against enzymes producing reactive species: Lipoxygenase (LOX), Myeloperoxidase (MPO), NAD(P)H oxidase (NOX), and Xanthine Oxidase (XOD). Affinity to enzymes decreased in the order: XOD > LOX > NOX > MPO.
（）-3-（1-（（2-羟基苯基）氨基）亚乙基）-2,4-二氧代色满-7-基乙酸酯（），（）-3-（1-（（3-羟基苯基）氨基）亚乙基）-2,4-二氧代色满-7-基乙酸酯（）和（）-3-（1-（（4-羟基苯基）氨基）亚乙基）-2,4-二氧代色满-7-基乙酸酯（），以对抗 HOO•/O2•-自由基。研究包括电子自旋共振（ESR）测量和 DFT 动力学研究。在生理条件下，使用基于量子力学的整体自由基清除活性测试（QM-ORSA）评估了抗氧化机制-形式氢原子转移（-HAT）、自由基加合物形成（RAF）、顺序质子损失后电子转移（SPLET）和单电子转移后质子转移（SET-PT）的热力学和动力学参数。ESR 结果表明，抗氧化活性按以下顺序降低：（58.7%）>（57.5%）>（53.1%）。动力学分析表明，-HAT 机制主导了 HOO 的失活。新提出的顺序质子损失后自由基加合物形成（SPL-RAF）机制描述了与 O 的相互作用。对 O 的活性为（1.26×10 Ms）>（7.71×10 Ms）>（4.22×10 Ms）。分子对接和动力学研究测试了对产生活性物质的酶的抑制能力：脂氧合酶（LOX）、髓过氧化物酶（MPO）、NAD（P）H 氧化酶（NOX）和黄嘌呤氧化酶（XOD）。对酶的亲和力按以下顺序降低：XOD>LOX>NOX>MPO。
