title: Evaluation of anti-HCV activity and SAR study of (+)-lycoricidine through targeting of host heat-stress cognate 70 (Hsc70).
abstract: The anti hepatitis C virus (HCV) activity of (+)-lycoricidine (1) was evaluated for the first time in this letter, yielding an EC50 value of 0.55 nmol/mL and an selection index (SI) value of 12.72. Further studies indicated that 1 induced this effect by down-regulating host heat-stress cognate 70 (Hsc70) expression. In addition, 20 derivatives were designed and synthesised to investigate the basic structure-activity relationship (SAR) of the title compound. Several of these derivatives exhibit a good inhibition of HCV, such as compound 3 (EC50=0.68 nmol/mL, SI=33.86), compound 2d (EC50=15 nmol/mL, SI=12) and compound 5 (EC50=33 nmol/mL, SI >10.91). Meanwhile, the experimental data suggest that the modification of certain groups of (+)-lycoricidine can reduce the cytotoxicity of the compounds.
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China.
authors.forename: Duo-Zhi
authors.initials: DZ
authors.lastname: Chen
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Jiang
authors.forename: Ke-Qing
authors.initials: KQ
authors.lastname: Zhang
authors.forename: Hong-Ping
authors.initials: HP
authors.lastname: He
authors.forename: Ying-Tong
authors.initials: YT
authors.lastname: Di
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jie-Yun
authors.initials: JY
authors.lastname: Cai
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Shun-Lin
authors.initials: SL
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Yi
authors.forename: Zong-Gen
authors.initials: ZG
authors.lastname: Peng
authors.forename: Xiao-Jiang
authors.initials: XJ
authors.lastname: Hao
mesh_terms: D047151:Amaryllidaceae Alkaloids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects; D050883:HSC70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D010617:Phenanthridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D047151:Amaryllidaceae Alkaloids; D000998:Antiviral Agents; D050883:HSC70 Heat-Shock Proteins; D010617:Phenanthridines; C500283:lycoricidine