Pontiki E, Hadjipavlou-Litina D
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Bioorg Med Chem. 2007 Sep 1;15(17):5819-27. doi: 10.1016/j.bmc.2007.06.001. Epub 2007 Jun 7.
Lipoxygenase catalyzes the first two steps of the transformation of arachidonic acid into leukotrienes which are implicated in host defense reactions. It is well known that many acids possess potent anti-inflammatory activity. Taking into account that compounds bearing a thienyl, naphthyl, pyrollyl, and 2,4-di-tert-butyl-phenol moieties possess anti-inflammatory activity which is related to their capacity to transfer electrons and to scavenge reactive oxygen species, we synthesized some new aryl-acetic acids and we explored their ability to inhibit soybean lipoxygenase, to present antioxidant and anti-inflammatory activities, and to interact with glutathione. The compounds have shown important antioxidant activity, medium anti-inflammatory activity, and very good inhibition of soybean lipoxygenase. Compound 3-(3,5-di-tert-butyl-2-hydroxy-phenyl)-2-phenyl-acrylic acid (1i) showed significant in vitro LO inhibition (IC(50) 65 microM). The results are discussed in terms of structural and physicochemical characteristics of the compounds. The structures of the synthesized compounds were confirmed by spectral and elemental analysis. Their lipophilicity are experimentally determined by RPTLC method.
脂氧合酶催化花生四烯酸转化为白三烯的前两步反应，白三烯参与宿主防御反应。众所周知，许多酸具有强大的抗炎活性。考虑到带有噻吩基、萘基、吡咯基和2,4-二叔丁基苯酚部分的化合物具有抗炎活性，这与其转移电子和清除活性氧的能力有关，我们合成了一些新的芳基乙酸，并研究了它们抑制大豆脂氧合酶的能力、呈现抗氧化和抗炎活性以及与谷胱甘肽相互作用的能力。这些化合物表现出重要的抗氧化活性、中等抗炎活性以及对大豆脂氧合酶的良好抑制作用。化合物3-(3,5-二叔丁基-2-羟基苯基)-2-苯基丙烯酸（1i）在体外显示出显著的脂氧合酶抑制作用（IC(50) 65 microM）。根据化合物的结构和物理化学特性对结果进行了讨论。通过光谱和元素分析确认了合成化合物的结构。通过反相薄层色谱法实验测定了它们的亲脂性。
