多巴胺-羟基肉桂酸孪合抗氧化剂的稳定性,正常细胞毒活性以及自由基清除活性的饱和效应（英文）

本论文合成了多巴胺(DA)和羟基肉桂酸(HCAs)的孪合抗氧化剂(2a–e),即肉桂酰多巴(2a),对香豆酰多巴(2b),咖啡酰多巴(2c),阿魏酰多巴(2d),芥子酰多巴(2e)。所有化合物在p H 1.3,p H 5.0的缓冲液中非常稳定,在p H 7.4的缓冲液中可发生水解。在人血浆中,化合物水解反应进行更快,其水解顺序以半衰期表示:2c(1.21 h)<2e(1.52 h)<2d(1.85 h)<2b(3.38 h)<2a(3.88 h)。稳定性结果表明,化合物具有的供电子取代基越多,其稳定性越低。通过紫外光谱证实了,因为化合物2c,2d,和2e具有更多的羟基和甲氧基取代基,所以相比于2a和2b,产生了50 nm的红移。此外,在浓度40μM和作用时间48 h时,化合物2b–e和DA对人正常HUVEC细胞未表现出毒性,而2a表现了16%的增值抑制作用。通过ABTS?+和超氧阴离子分析,所有化合物均表现出了比水溶性维生素E(trolox)更高的抗氧化活性。有趣的是,孪合物2a–e的抗氧化活性高于HCAs,而低于或者相当于DA的活性。因此,孪合分子的抗氧化活性可能存在"饱和度"。

Stability,cytotoxicity, and saturation effect of the free radical-scavenging cinnamic acid-dopamine hybrid antioxidants

Hybrid antioxidants cinnamoyldopamine (2a), p-coumaroyldopamine (2b), caffeoyldopamine (2c), feruloyldopamine (2d) and sinapoyldopamine (2e) were synthesized by conjugation of dopamine (DA) and hydroxycinnamic acids (HCAs). The stabilities were studied in buffers at pH 1.3, pH 5.0, and pH 7.4 including the human plasma. All the compounds were found highly stable at acidic pH, but underwent hydrolysis at neutral pH. Furthermore, the hydrolysis proceeded much faster in plasma in the following order as indicated by half-life values (t_1/2), 2c (1.21 h)<2e (1.52 h)<2d (1.85 h)<2b (3.38 h)<2a (3.88 h), correlating with the number of electron-donating groups. It has been proven by UV spectrum that 2c, 2d, and 2e displayed red shift of more than 50 nm as compared to 2a and 2b, because of the presence of OH and OCH₃ groups. In addition, the compounds (2b–e) showed no cytotoxicity on normal HUVEC cells as DA, although 2a displayed a 16% inhibition of proliferation at 40 μM following 48 h incubation. Their free radical-scavenging activities were evaluated using ABTS^•+ and superoxide anion assays and the mechanisms were proposed. It was found that they all exhibited higher activities than trolox, a recognized antioxidant. Amazingly, in the case of the hybrids (2a–e), their activity was higher than that of HCAs while lower or comparable to that of DA, suggesting that there may be a “saturation effect” with the hybrid molecules in the antioxidant activities.