在单一药剂中平衡抗氧化，降血脂和抗炎活性：2-羟基-2-取代的吗啉，1,4-苯并恶嗪和1,4-苯并噻嗪衍生物作为治疗动脉粥样硬化的合理治疗方法的实例

Title:Balancing Antioxidant, Hypolipidemic and Anti-inflammatory Activity in a Single Agent: The Example of 2-Hydroxy-2-Substituted Morpholine, 1,4-Benzoxazine and 1,4-Benzothiazine Derivatives as a Rational Therapeutic Approach against Atherosclerosis

Volume: 24 Issue: 12

关键词: 设计，合成，氧化应激，脂质过氧化，微粒体，低密度脂蛋白氧化，角鲨烯合酶抑制剂，环氧合酶-1和-2抑制剂，甘油三酯，总胆固醇，低密度脂蛋白胆固醇，高密度脂蛋白胆固醇，动脉粥样硬化，高脂饮食，多功能药物。

摘要: In line with our previous studies, novel morpholine and benzoxa(or thia)zine lead compounds have been developed through a rational design that modulate a multiplicity of targets against atherosclerosis. We have evaluated the most promising compounds for their efficiency to a) intercept and scavenge free radicals, b) inhibit the metal ion (Cu2+)- induced LDL oxidation c) act intracellularly as antioxidants in THP-1 monocytes from a leukemic patient and d) inhibit the pro-inflammatory enzymes cyclooxygenase-1 (COX-1) and -2 (COX-2) in vitro. Furthermore, two representative compounds were tested for their potential to decrease lipidemic parameters (TC, LDL and TG) in hyperlipidemic mice. Most derivatives indicated a remarkable antioxidant activity, while at the same time exhibited a significant in vitro anti-inflammatory activity, inhibiting COX-1 or/and COX-2 activity at 20 μΜ. In addition, after their long-term administration, compounds 6 and 8 afforded considerable activity in a chronic experimental animal model of hyperlipidemia (after high fat diet administration). The multifunctional pharmacological profile exhibited by the compounds of this study renders them interesting lead compounds for the development of novel agents against atherosclerosis.

Cite this article as:

Balancing Antioxidant, Hypolipidemic and Anti-inflammatory Activity in a Single Agent: The Example of 2-Hydroxy-2-Substituted Morpholine, 1,4-Benzoxazine and 1,4-Benzothiazine Derivatives as a Rational Therapeutic Approach against Atherosclerosis, Current Medicinal Chemistry 2017; 24 (12) . https://dx.doi.org/10.2174/0929867323666160814001803