Sasaki Kazue, Minowa Nobuto, Kuzuhara Hiroyuki, Nishiyama Shoji
Medicinal Chemistry Research Laboratory, Pharmaceutical Research Department, Meiji Seika Kaisha, Ltd., 760 Morooka-cho, Yokohama 222-8567, Japan.
Bioorg Med Chem. 2005 Aug 15;13(16):4900-11. doi: 10.1016/j.bmc.2005.04.074.
To shed light on the structure-activity relationship, various soyasapogenol B derivatives were synthesized and evaluated for preventive effects on liver injury in the concanavalin A (Con A)-induced hepatitis model in mice. Con A injection into mice induces some pathophysiology of human liver disease such as autoimmune or viral hepatitis. Two hydroxyl groups on the A ring of soyasapogenol B are required for amelioration of liver damage. Modification of the C-22 hydroxyl moiety with an acyloxy or alkyloxy group, or removal of the hydroxyl group, resulted in a greatly enhanced percentage of alleviation. Among the series of soyasapogenol B derivatives examined, six compounds exhibited preventive effects on liver damage.
为了阐明构效关系,合成了多种大豆皂醇B衍生物,并在刀豆蛋白A(Con A)诱导的小鼠肝炎模型中评估了它们对肝损伤的预防作用。向小鼠注射Con A会诱发一些人类肝脏疾病的病理生理过程,如自身免疫性或病毒性肝炎。大豆皂醇B的A环上的两个羟基对于改善肝损伤是必需的。用酰氧基或烷氧基修饰C-22羟基部分,或去除羟基,会使缓解百分比大大提高。在所研究的一系列大豆皂醇B衍生物中,有六种化合物对肝损伤表现出预防作用。