title: Boronic Acid Modifications Enhance the Anti-Influenza A Virus Activities of Novel Quindoline Derivatives.
abstract: The unique glycan-binding ability of chemically synthesized boronic acid derivatives makes them emerging candidates for developing anti-influenza A virus (IAV) drugs. Herein we report the synthesis and the anti-IAV activities of three series of novel boronic acid-modified quindoline derivatives both in vitro and in vivo. Boronic acid-modified compounds 6a and 7a effectively prevented the entry of virus RNP into the nucleus, reduced virus titers in IAV infected cells, and also inhibited the activity of viral neuraminidase. Compound 7a possessed broad antiviral spectrum and was able to inhibit cellular NF-κB and MAPK signaling pathways to block IAV infection. More importantly, IAV infected mice treated with compound 7a showed better survival rates than mice treated with oseltamivir, a popular anti-IAV drug. Thus, our study provides not only an antiviral preclinical candidate but also useful information for further research and development of boronic acid-modified anti-IAV drugs.
authors.affiliation: Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China , Qingdao 266003, P. R. China.|Marine Biomedical Research Institute of Qingdao , Qingdao 266003, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China , Qingdao 266003, P. R. China.|Marine Biomedical Research Institute of Qingdao , Qingdao 266003, P. R. China.
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Yin
authors.affiliation: Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China , Qingdao 266003, P. R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China , Qingdao 266003, P. R. China.|Marine Biomedical Research Institute of Qingdao , Qingdao 266003, P. R. China.
authors.forename: Rilei
authors.initials: R
authors.lastname: Yu
authors.affiliation: Institute of Cerebrovascular Diseases, Affiliated Hospital of Qingdao University Medical College , Qingdao, 266003, P. R. China.
authors.forename: Cui
authors.initials: C
authors.lastname: Hao
authors.affiliation: Institute of Cerebrovascular Diseases, Affiliated Hospital of Qingdao University Medical College , Qingdao, 266003, P. R. China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China , Qingdao 266003, P. R. China.|Marine Biomedical Research Institute of Qingdao , Qingdao 266003, P. R. China.|Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology , Qingdao, 266237, P. R. China.
authors.forename: Tao
authors.identifier: 0000-0002-6590-5041
authors.initials: T
authors.lastname: Jiang
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D001897:Boronic Acids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D005260:Female; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D009980:Influenza A virus / Q000187:drug effects* / Q000276:immunology; D007251:Influenza, Human / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000470:Alkaloids; D000998:Antiviral Agents; D001897:Boronic Acids; D007211:Indoles; D016328:NF-kappa B; D011804:Quinolines; C016712:quindoline