Gazák Radek, Svobodová Alena, Psotová Jitka, Sedmera Petr, Prikrylová Vera, Walterová Daniela, Kren Vladimír
Institute of Microbiology, Academy of Sciences of the Czech Republic, Laboratory of Biotransformation, Vídenská 1083, CZ-142 20 Prague, Czech Republic.
Bioorg Med Chem. 2004 Nov 1;12(21):5677-87. doi: 10.1016/j.bmc.2004.07.064.
Carboxylic acids derived from silybin (1) and 2,3-dehydrosilybin (2) with improved water solubility were prepared by selective oxidation of parent compounds and a new inexpensive method for preparation of 2,3-dehydrosilybin from silybin was developed and optimised. The antioxidative properties of the above-mentioned compounds and of side product 3a from oxidation of compound 1 were determined by cyclic voltammetry, free radical scavenging (DPPH, superoxide) assays, and by inhibition of in vitro generated liver microsomal lipid peroxidation. Dehydrogenation at C((2))-C((3)) in flavonolignans (silybin vs 2,3-dehydrosilybin; silybinic acid vs 2,3-dehydrosilybinic acid) strongly improved antioxidative properties (analogously as in flavonoids taxifolin vs quercetin). Thus, in antioxidative properties, dehydrosilybin was superior to silybin by one order, but its water solubility is too low for application in aqueous milieu. On the other hand, 2,3-dehydrosilybinic acid is a fairly soluble derivative with antilipoperoxidation and antiradical activities better than that of silybin.
通过对母体化合物进行选择性氧化制备了水溶解度提高的源自水飞蓟宾（1）和2,3 - 脱氢水飞蓟宾（2）的羧酸，并开发并优化了一种从水飞蓟宾制备2,3 - 脱氢水飞蓟宾的新的廉价方法。通过循环伏安法、自由基清除（DPPH、超氧化物）测定以及抑制体外产生的肝微粒体脂质过氧化作用，对上述化合物以及化合物1氧化的副产物3a的抗氧化性能进行了测定。黄酮木脂素中C（(2)）-C（(3)）处的脱氢反应（水飞蓟宾与2,3 - 脱氢水飞蓟宾；水飞蓟宾酸与2,3 - 脱氢水飞蓟宾酸）极大地改善了抗氧化性能（类似于黄酮类化合物中的紫杉叶素与槲皮素）。因此，在抗氧化性能方面，脱氢水飞蓟宾比水飞蓟宾高一个量级，但其水溶解度过低，无法应用于水性介质中。另一方面，2,3 - 脱氢水飞蓟宾酸是一种溶解度相当好的衍生物，其抗脂质过氧化和抗自由基活性优于水飞蓟宾。
