Evolution of matrinic ethanol derivatives as anti-HCV agents from matrine skeleton.
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 EC50value 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.
Beijing Key Laboratory of Anti-infective Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China.
Ying-Hong
YH
Li
Beijing Key Laboratory of Anti-infective Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China.
Zhou-Yi
ZY
Wu
Beijing Key Laboratory of Anti-infective Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China.
Sheng
S
Tang
Beijing Key Laboratory of Anti-infective Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China.
Xin
X
Zhang
Beijing Key Laboratory of Anti-infective Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China.
Yan-Xiang
YX
Wang
Beijing Key Laboratory of Anti-infective Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China.
Jian-Dong
JD
Jiang
Beijing Key Laboratory of Anti-infective Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China. Electronic address: pumcpzg@126.com.
Zong-Gen
ZG
Peng
Beijing Key Laboratory of Anti-infective Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China. Electronic address: songdanqingsdq@hotmail.com.
Dan-Qing
DQ
Song
D000470:Alkaloids / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D002460:Cell Line; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000431:Ethanol / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D016174:Hepacivirus / Q000187:drug effects* / Q000254:growth & development; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D011807:Quinolizines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D000093842:Matrines
D000470:Alkaloids; D000998:Antiviral Agents; D004365:Drugs, Chinese Herbal; D011807:Quinolizines; D000431:Ethanol; D000093842:Matrines
Druglike; Hepatitis C virus; Matrinic ethanol; Structure–activity relationship