高等学校化学学报

高等学校化学学报 ›› 2012, Vol. 33 ›› Issue (05): 969.doi: 10.3969/j.issn.0251-0790.2012.05.019

• 有机化学 • 上一篇    下一篇

齐墩果酸γ-内酯衍生物的合成及活性评价

钱珊1, 吴勇2, 何宇新1, 王周玉1, 杨文宇1, 陈欣3   

  1. 1. 西华大学生物工程学院, 成都 610039;
    2. 四川大学华西药学院, 成都 610041;
    3. 成都地奥新药筛选中心, 成都 610041
  • 收稿日期:2011-06-22 出版日期:2012-05-10 发布日期:2012-05-10
  • 作者简介:钱 珊, 女, 博士, 讲师, 主要从事天然产物结构修饰及活性研究. E-mail: qians33@163.com
  • 基金资助:

    四川省科技厅应用基础项目(批准号: 2010JY0119), 四川省教育厅青年项目(批准号: 11205023)和西华大学重点科研基金项目(批准号: Z1020519)资助.

Synthesis and Biological Evaluation of Oleanane Triterpenoid with γ-Lactone Functionality in Ring C

QIAN Shan1, WU Yong2, HE Yu-Xin1, WANG Zhou-Yu1, YANG Wen-Yu1, CHEN Xin3   

  1. 1. School of Bioengineering, Xihua University, Chengdu 610039;
    2. West China School of Pharmacy, Sichuan University, Chengdu 610041;
    3. Drug Screening Center, DiAo Pharmaceutical Group, Chengdu 610041, China
  • Received:2011-06-22 Online:2012-05-10 Published:2012-05-10

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摘要： 对齐墩果酸(OA)的C环进行结构修饰, 合成了含有γ-内酯结构的OA衍生物, 并针对12个常见疾病的蛋白质靶点或细胞进行了体外生物活性筛选. 其中部分化合物结构中引入了水溶性基团, 如形成糖苷或引入酸性基团, 提高了生物利用度. 活性筛选结果表明, 内酯化合物13对组织蛋白酶K显示出很好的抑制活性(IC50=3.58 μg/mL), 可作为抗骨质疏松药物的先导化合物. 初步构效关系分析表明, 该化合物的γ-内酯结构和糖链片段为活性基团.

关键词: 齐墩果酸, 组织蛋白酶K, 骨质疏松症, 构效关系

Abstract: Some oleanolic acid(OA) derivatives with γ-lactone functionality in ring C had better H2O solubi-lity and bioavailability than OA. Preliminary biological screening in vitro of these derivatives for 12 responding protein targets and cells of frequent diseases was processed. This investigation revealed that lactone 13 showed significant activity(IC50=3.58 μg/mL) against Cathepsin K, and was found to be a potent leader compound for the treatment of osteoporosis. Preliminary structure-activity relationship analysis indicated that the γ-lactone and glyco-groups were active groups.

Key words: Oleanolic acid, Cathepsin K, Osteoporosis, Structure-activity relationship

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