University of Saint-Esprit de Kaslik, Faculty of Sciences and Computer Engineering, B.P. 446 Jounieh, Lebanon.
Biopharm Drug Dispos. 2009 Oct;30(7):389-97. doi: 10.1002/bdd.673.
It was shown previously that the anticancerous cytotoxic oxygenated triterpenes, cucurbitacin E (Cuc E) and its deacetylated form, cucurbitacin I (Cuc I), interacted differently with human serum albumin. In this study, the biochemical stability of Cuc E was investigated in vitro by reverse-phase high performance liquid chromatography. The hydrolysis rate in acidic and alkaline solutions, and in enzymatic conditions in human plasma and in purified plasma esterase solutions of butyrylcholinesterase and albumin, was compared with that measured in phosphate buffer saline (pH 7.4). Cuc E hydrolysis was detected in all the in vitro tests, but the extent of hydrolysis varied according to the different enzymatic and non-enzymatic conditions. A remarkable rapid hydrolysis of Cuc E was detected in acidic and alkaline solutions. A significant rate of hydrolysis of Cuc E was monitored in human plasma and was associated with the detection of Cuc I. The stability of Cuc E was greatly enhanced in the presence of albumin. However, purified butyrylcholinesterase had no effect on Cuc E stability. Among specific inhibitors of plasma esterases, only EDTA increased Cuc E stability, suggesting that paraoxonase is the human plasma esterase involved in the hydrolysis of Cuc E.
先前的研究表明，具有抗癌细胞毒性的含氧三萜类化合物葫芦素 E（Cuc E）及其去乙酰化形式葫芦素 I（Cuc I）与人血清白蛋白的相互作用方式不同。在这项研究中，通过反相高效液相色谱法体外研究了 Cuc E 的生化稳定性。比较了 Cuc E 在酸性和碱性溶液中的水解率、人血浆中和纯化的血浆酯酶（丁酰胆碱酯酶和白蛋白）溶液中的酶解条件下的水解率，以及在磷酸盐缓冲盐水（pH 7.4）中的水解率。在所有的体外试验中都检测到了 Cuc E 的水解，但水解的程度因不同的酶解和非酶解条件而有所不同。在酸性和碱性溶液中检测到 Cuc E 的快速水解。在人血浆中监测到 Cuc E 的显著水解速率，并与 Cuc I 的检测相关。在白蛋白存在下，Cuc E 的稳定性大大增强。然而，纯化的丁酰胆碱酯酶对 Cuc E 的稳定性没有影响。在血浆酯酶的特定抑制剂中，只有 EDTA 增加了 Cuc E 的稳定性，表明对氧磷酶是参与 Cuc E 水解的人血浆酯酶。
