Design,Synthesis And Biological Evaluation Of Oxime Derivatives For Anti-hepatitis B Virus With Virtual Dual-target

Hepatitis B virus(HBV)infection is one of the serious infectious diseases that is chronic harm to human health in the world.So many pharmaceutical and chemical researchers have focused to find new anti-hepatitis B drugs.Drugs used in clinical treatment of chronic hepatitis B include nucleoside analogues and interferons.Expensive cost of treatment with interferons and resistance from long-term treatment with nucleosides limited drugs used in anti-HBV treatments.Therefore,inventions of new and effective anti-HBV agents are very significant,and it promotes us to focus on finding anti-HBV active compounds.A series of oxime derivatives are virtual screened with human leukocyte antigen HLA-A*02:03(PDB ID 30X8)and HLA-A*1101(PDB ID 2HN7)as dual-target by the Molecular Operating Environment(MOE)software.24 unreported compounds including 8 oxime compounds and 16 oxime ether compounds were synthesized with benzene,toluene,metoxybenzene and chlorobenzene as initial raw materials,and their structures were elucidated by 1H NMR,13CNMR and MS data.These compounds were assayed with HepG 2.2.15cell line in vitro to evaluate their anti-HBV activities.Inhibition of secreting HBV surface antigen(HBsAg)and e antigen(HBeAg)were used to evaluate anti-HBV activities of these compounds.Results showed that some of compounds displayed more anti-HBV activity than the control(lamivudine)in inhibiting HBsAg and HBeAg.Compounds 4B-2,4D-2 and 4B-3 which displayed more anti-HBV activities than others,showed inhibitory effect on secretion of HBsAg IC50=63.85 ?M,67.65 ?M,78.46 ?M respectively and HBeAg IC50=49.39 ?M,85.10 ?M,84.57 ?M respectively.Investigations on relationship of structure-activity showed methyl oxirne ethers possessed more obvious anti-HBV activity.