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Evolution of matrinic ethanol derivatives as anti-HCV agents from matrine skeleton
Ying-Hong Li1, Zhou-Yi Wu1, Sheng Tang1
1Beijing Key Laboratory of Anti-infective Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China.
Abstract:
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 EC50 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.
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