Design,Synthesis And Biological Evaluation Of Oleanolic Acid-C3 Glycoconjugate As Influenza Inhibitors

Influenza A virus(IAV)is one of the major public health threats worldwide.With the emergence of drug-resistant virus strains,new and effective anti-IAV drugs are urgently needed.The development of drugs for the entry of viruses can inhibit the infection of influenza viruses at the source,so it has become a hot spot for the development of antiviral drugs.Influenza virus glycoprotein hemagglutinin(HA)plays an important role in the early stage of virus infection in host cells,so HA is a potential target for the development of anti-influenza drugs.The previous research of the research group showed that natural products such as oleanolic acid(oleanolic acid,OA)can effectively bind to hemagglutinin protein and inhibit the entry of influenza virus into host cells,thereby exerting antiviral effect.However,previous studies have mainly focused on the structural modification of the C-28 carboxyl group of OA,and there are few studies on the structure-activity relationship of the OA-C3 anti-influenza virus.Therefore,in this paper,OA is used as the parent nucleus,based on the previous research basis,the OA-C3 position is glycosylated,and 24 compounds have been designed and synthesized.Activity evaluation,systematically studied the structure-activity relationship of this kind of compound to inhibit influenza virus.We found that compound L6 a,namely OA-acetylgalactose conjugate,had no significant cytotoxicity to MDCK cells and had certain inhibition to influenza A effect.Studies on the molecular mechanism of anti-influenza virus against L6 a show that L6 a can effectively inhibit the hemagglutination of influenza A virus on chicken red blood cells,verifying that the possible target of L6 a is HA protein.The above studies have contributed to the development of pentacyclic triterpenoid derivatives as inhibitors of influenza viruses.