Design, Synthesis and Structure-Activity Relationship Optimization of Lycorine Derivatives for HCV Inhibition

doi:10.1038/srep14972

	Design, Synthesis and Structure-Activity Relationship Optimization of Lycorine Derivatives for HCV Inhibition
	Chen,Duozhi; Cai,Jieyun; Cheng,Junjun; Jing,Chenxu; Yin,Junlin; Jiang,Jiandong; Peng,Zonggen; Hao,Xiaojiang
	2015-10-07
发表期刊	SCIENTIFIC REPORTS
卷号	5
摘要	Lycorine is reported to be a multifunctional compound. We previously showed that lycorine is an HCV inhibitor with strong activity. Further research on the antivirus mechanism indicated that lycorine does not affect the enzymes that are indispensable to HCV replication but suppresses the expression of Hsc70 in the host cell to limit HCV replication. However, due to the cytotoxicity and apoptosis induction of lycorine, lycorine is unsafe to be a anti-HCV agent for clinical application. As a result of increasing interest, its structure was optimized for the first time and a novel series of lycorine derivatives was synthesized, all of which lost their cytotoxicity to different degrees. Structure-activity analysis of these compounds revealed that disubstitution on the free hydroxyl groups at C1 and C2 and/or degradation of the benzodioxole group would markedly reduce the cytotoxicity. Furthermore, an alpha, beta-unsaturated ketone would improve the HCV inhibitory activity of lycorine. The C3-C4 double bond is crucial to the anti-HCV activity because hydrogenation of this double bond clearly weakened HCV inhibition.
DOI	10.1038/srep14972
收录类别	SCI
语种	英语
WOS记录号	WOS:000362346700001
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/25173
专题	植物化学与西部植物资源持续利用国家重点实验室
推荐引用方式 GB/T 7714	Chen,Duozhi,Cai,Jieyun,Cheng,Junjun,et al. Design, Synthesis and Structure-Activity Relationship Optimization of Lycorine Derivatives for HCV Inhibition[J]. SCIENTIFIC REPORTS,2015,5.
APA	Chen,Duozhi.,Cai,Jieyun.,Cheng,Junjun.,Jing,Chenxu.,Yin,Junlin.,...&Hao,Xiaojiang.(2015).Design, Synthesis and Structure-Activity Relationship Optimization of Lycorine Derivatives for HCV Inhibition.SCIENTIFIC REPORTS,5.
MLA	Chen,Duozhi,et al."Design, Synthesis and Structure-Activity Relationship Optimization of Lycorine Derivatives for HCV Inhibition".SCIENTIFIC REPORTS 5(2015).

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