Synthesis And Bioactive Investigation Of Benzoxazole Based Shikimamide Derivatives

Hepatitis B is a global infectious disease that causes results approximately600000 deaths annually.Currently,the drugs for treating hepatitis B virus include subcutaneous interferon（IFN）and oral nucleoside analogues（NUCs）.Long term treatment of HBV has led many side effects and drug resistance,and decrease effectivities of these drugs.For improving effectivities of anti-HBV therapy,it is nessissary to develop new anti HBV drugs.Shikimic acid widely found in natural products,arebioactive for anti-inflammatory,antibacterial,antitumor,antiviral,immunomodulatory,herbicidal,and so on.Isoxazoles are bioactive compounds.Combination of shikimic acid and isoxazoles may generate new bioactive agents.On the basis of bioactive of shikimic acid and isoxazole compounds,we designed benzisoxazolyl shikimic amides then these desighed compounds were docked with HBV core protein（PDB ID 3KXS）.Results showed all desighed compounds strongly bound to the protein.22 new isoxazole derivatives were designed and synthesized,and their structures were determined by ¹ HNMR,¹³CNMR,and MS methods.Assay of these compounds for bioactive of antibacterial and inhibiting hepatitis B virus in vitro were carried out.Results showed these compounds were less toxic,and among them compounds 11,14,15,and 17 had significant inhibitory effects on the secretion of HBe Ag and HBs Ag of hepatitis B virus.The compounds showed different antibacterial activities against Gram-positive bacteria（Staphylococcus aureus,Bacillus subtilis）and Gram-negative bacteria（Escherichia coli,Pseudomonas aeruginosa）.