合成香豆素-异恶唑-吡啶杂化物的药物化学研究
Pharmacochemical Studies of Synthesized Coumarin-Isoxazole-Pyridine Hybrids.
作者信息
Douka Matina D, Sigala Ioanna M, Gabriel Catherine, Nikolakaki Eleni, Hadjipavlou-Litina Dimitra J, Litinas Konstantinos E
机构信息
Laboratory of Organic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Laboratory of Biochemistry, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
出版信息
Molecules. 2025 Apr 2;30(7):1592. doi: 10.3390/molecules30071592.
Several new coumarin-isoxazole-pyridine hybrids were synthesized through a 1,3-dipolar cycloaddition reaction of nitrile oxides, prepared in situ from pyridine aldehyde oximes, with propargyloxy- or propargylaminocoumarins in moderate-to-good yields. Synthetic modifications were applied using (diacetoxyiodo)benzene (PIDA) at room temperature, microwave irradiation, or tert-butyl nitrite (TBN) under reflux. Coumarin, isoxazole, and pyridine groups were selected for hybridization in one molecule due to their biological impact to inhibit lipid peroxidation and an enzyme implicated in inflammation. Preliminary in vitro screening tests for lipoxygenase (LOX) inhibition and anti-lipid peroxidation for the new hybrids were performed. A discussion on the structure-activity relationship is presented. Compounds and were found to be potent LOX inhibitors with IC 5 μΜ and 10 μΜ, respectively, while presented high (90.4%) anti-lipid peroxidation. Furthermore, hybrids and exhibited moderate-to-low anticancer activities on HeLa, HT-29, and H1437 cancer cells.
通过由吡啶醛肟原位制备的腈氧化物与炔丙氧基香豆素或炔丙基氨基香豆素进行1,3-偶极环加成反应，以中等到良好的产率合成了几种新型香豆素-异恶唑-吡啶杂化物。使用（二乙酰氧基碘）苯（PIDA）在室温下、微波辐射或亚硝酸叔丁酯（TBN）在回流条件下进行合成修饰。由于香豆素、异恶唑和吡啶基团对抑制脂质过氧化和一种与炎症有关的酶具有生物学影响，因此选择将它们杂化在一个分子中。对新杂化物进行了脂氧合酶（LOX）抑制和抗脂质过氧化的初步体外筛选试验。给出了关于构效关系的讨论。发现化合物 和 分别是有效的LOX抑制剂，IC50分别为5 μΜ和10 μΜ，而 表现出高的（90.4%）抗脂质过氧化活性。此外，杂化物 和 对HeLa、HT-29和H1437癌细胞表现出中等到低的抗癌活性。
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