Li Ying-Hong, Wu Zhou-Yi, Tang Sheng, Zhang Xin, Wang Yan-Xiang, Jiang Jian-Dong, Peng Zong-Gen, Song Dan-Qing
Beijing Key Laboratory of Anti-infective Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China.
Beijing Key Laboratory of Anti-infective Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China.
Bioorg Med Chem Lett. 2017 May 1;27(9):1962-1966. doi: 10.1016/j.bmcl.2017.03.025. Epub 2017 Mar 11.
Twenty-two novel 12N-substituted matrinic ethanol derivatives were synthesized and evaluated for their antiviral activities against HCV taking compound 1 as the lead. The SAR study indicated that the shortening of the 11-butyl chain to ethyl chain did not affect the activity significantly. Out of the target compounds, matrinic ethanol 6a demonstrated a potential anti-HCV effect with an EC value of 3.2μM and a SI value of 96.6. The free hydroxyl arm in 6a made it possible as a parent structure to prepare pro-drug for the potential application in HCV treatment. This study provided powerful information on further strategic optimization and development of this kind of compounds into a novel family of anti-HCV agents.
以化合物1为先导，合成了22种新型12N-取代苦参醇衍生物，并对其抗丙型肝炎病毒（HCV）活性进行了评价。构效关系研究表明，将11-丁基链缩短为乙基链对活性影响不大。在目标化合物中，苦参醇6a表现出潜在的抗HCV作用，其半数有效浓度（EC）值为3.2μM，选择性指数（SI）值为96.6。6a中的游离羟基臂使其有可能作为母体结构制备前药，用于HCV治疗的潜在应用。本研究为进一步对这类化合物进行战略优化并将其开发成新型抗HCV药物家族提供了有力信息。
