Background: From the point of view of medicinal chemistry, compounds containing phenolic and pyrazolic moiety are significant since they are often constituents of bioactive compounds.

Objective: The aims of this study were to synthesize pyrazole derivatives of medically relevant phenolic acids, confirm their structure, and evaluate their antioxidative and anti-LOX activities.

Methods: Phenolic pyrazole derivatives were obtained, starting from esters of medically relevant phenolic acids. The structures of all obtained compounds were determined by NMR and IR spectroscopy, and UV-Vis spectrophotometry. In addition, the single-crystal X-ray diffraction was used. Pyrazole derivatives were tested for their in vitro antioxidative (DPPH assay), and lipoxygenase (LOX) inhibitory activities. Radical quenching mechanism was estimated using DFT and thermodynamic approach, while molecular docking was used to estimate the binding mode within the enzyme.

Results: Pyrazole derivatives were obtained in high yields. The crystal structure of a new compound 3e was determined. Pyrazole derivative with catechol moiety 3d exhibited excellent radical scavenging activity, while compound 3b exhibited the best anti-LOX activity. Molecular docking study revealed that there is no direct interaction of any ligand with the active site of LOX-Ib, but pyrazoles 3a-e behave as inhibitors blocking the approach of linoleic acid to the active site.

Conclusion: In this research, protocatechuic and vanillic acid pyrazole derivatives have been obtained for the first time. In vitro antioxidative assay suggests that pyrazole derivate of protocatechuic acid is a powerful radical scavenger, while anti-LOX assay indicates a pyrazole derivative with 4-hydroxyphenyl moiety.

背景：从药物化学的角度来看，含有酚类和吡唑类部分的化合物很重要，因为它们通常是生物活性化合物的成分。

目的：本研究的目的是合成医学相关酚酸的吡唑衍生物，确认其结构，并评估其抗氧化和抗 LOX 活性。

方法：从医学相关酚酸的酯开始，获得酚类吡唑衍生物。所有获得的化合物的结构均通过NMR和IR光谱以及UV-Vis分光光度法测定。此外，还使用了单晶 X 射线衍射。测试了吡唑衍生物的体外抗氧化（DPPH 测定）和脂肪氧化酶（LOX）抑制活性。使用 DFT 和热力学方法估计自由基猝灭机制，而分子对接用于估计酶内的结合模式。

结果：以高产率获得吡唑衍生物。确定了新化合物3e的晶体结构。具有邻苯二酚部分3d的吡唑衍生物表现出优异的自由基清除活性，而化合物3b表现出最好的抗LOX活性。分子对接研究表明，没有任何配体与 LOX-Ib 的活性位点直接相互作用，但吡唑 3a-e 充当抑制剂，阻止亚油酸接近活性位点。

结论：本研究首次获得原儿茶酸和香草酸吡唑衍生物。体外抗氧化试验表明原儿茶酸的吡唑衍生物是一种强大的自由基清除剂，而抗 LOX 试验表明吡唑衍生物具有 4-羟基苯基部分。