Theodosis-Nobelos Panagiotis, Athanasekou Chrysoula, Rekka Eleni A
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, Thessaloniki 54124, Greece.
Institute of Nanoscience & Nanotechnology, NCSR "Demokritos", 15310 Agia Paraskevi Attikis, Athens, Greece.
Bioorg Med Chem Lett. 2017 Nov 1;27(21):4800-4804. doi: 10.1016/j.bmcl.2017.09.054. Epub 2017 Sep 28.
Novel amide derivatives of trolox, 3,5-di-tert-butyl-4-hydroxybenzoic acid, (E)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)acrylic acid and cinnamic acid with cysteamine and l-cysteine ethyl ester were synthesised. In four cases, the disulfide derivatives were also isolated and tested. All compounds were examined for antioxidant activity, expressed as their ability to inhibit lipid peroxidation and to scavenge free radicals. They were found to demonstrate up to 17-fold better activity than that of the parent antioxidant acids. They could reduce acute inflammation up to 87%. The most active antioxidant compounds were further tested for their in vivo hypolipidemic effect, which ranged from 47% to 73%, and for their ability to protect the liver against oxidative toxicity caused by high paracetamol dose. The disulfide derivatives of 3,5-di-tert-butyl-4-hydroxybenzoic acid and cinnamic acid had no antioxidant activity and presented equal or lower anti-inflammatory effect than their thiol analogues, indicating that their molecular characteristics may not permit biological barrier penetration.
合成了生育三烯酚、3,5-二叔丁基-4-羟基苯甲酸、（E）-3-（3,5-二叔丁基-4-羟基苯基）丙烯酸和肉桂酸与半胱胺和L-半胱氨酸乙酯的新型酰胺衍生物。在四种情况下，还分离并测试了二硫键衍生物。对所有化合物进行了抗氧化活性检测，以其抑制脂质过氧化和清除自由基的能力来表示。发现它们的活性比母体抗氧化酸高17倍。它们能将急性炎症减轻高达87%。对活性最高的抗氧化化合物进一步测试了其体内降血脂作用（范围为47%至73%）以及保护肝脏免受高剂量扑热息痛引起的氧化毒性的能力。3,5-二叔丁基-4-羟基苯甲酸和肉桂酸的二硫键衍生物没有抗氧化活性，且抗炎效果与其硫醇类似物相当或更低，这表明它们的分子特性可能不允许穿透生物屏障。
