%0 Journal Article
%T Evaluation of anti-HCV activity and SAR study of (+)-lycoricidine through targeting of host heat-stress cognate 70 (Hsc70).
%A Chen DZ
%A Jiang JD
%A Zhang KQ
%A He HP
%A Di YT
%A Zhang Y
%A Cai JY
%A Wang L
%A Li SL
%A Yi P
%A Peng ZG
%A Hao XJ
%J Bioorg Med Chem Lett
%V 23
%N 9
%D May 2013 1
%M 23511018
%F 2.94
%R 10.1016/j.bmcl.2013.02.089
%X 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.