title: Design, synthesis, and in vitro biological evaluation of 1H-1,2,3-triazole-4-carboxamide derivatives as new anti-influenza A agents targeting virus nucleoprotein.
abstract: The influenza virus nucleoprotein (NP) is an emerging target for anti-influenza drug development. Nucleozin (1) and its closely related derivatives had been identified as NP inhibitors displaying anti-influenza activity. Utilizing 1 as a lead molecule, we successfully designed and synthesized a series of 1H-1,2,3-triazole-4-carboxamide derivatives as new anti-influenza A agents. One of the most potent compounds, 3b, inhibited the replication of various H3N2 and H1N1 influenza A virus strains with IC(50) values ranging from 0.5 to 4.6 μM. Compound 3b also strongly inhibited the replication of H5N1 (RG14), amantidine-resistant A/WSN/33 (H1N1), and oseltamivir-resistant A/WSN/1933 (H1N1, 274Y) virus strains with IC(50) values in sub-μM ranges. Further computational studies and mechanism investigation suggested that 3b might directly target influenza virus A nucleoprotein to inhibit its nuclear accumulation.
authors.affiliation: Key Laboratory of Regenerative Biology and Institute of Chemical Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Avenue, Guangzhou 510530, People's Republic of China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Cheng
authors.forename: Junting
authors.initials: J
authors.lastname: Wan
authors.forename: Meng-I
authors.initials: MI
authors.lastname: Lin
authors.forename: Yingxue
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Lu
authors.forename: Jinsong
authors.initials: J
authors.lastname: Liu
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.forename: Jianxin
authors.initials: J
authors.lastname: Chen
authors.forename: Zhengchao
authors.initials: Z
authors.lastname: Tu
authors.forename: Yih-Shyun E
authors.initials: YS
authors.lastname: Cheng
authors.forename: Ke
authors.initials: K
authors.lastname: Ding
mesh_terms: D000547:Amantadine / Q000494:pharmacology; D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D004285:Dogs; D015195:Drug Design; D024882:Drug Resistance, Viral; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects; D009980:Influenza A virus / Q000187:drug effects* / Q000378:metabolism; D008958:Models, Molecular; D009698:Nucleoproteins / Q000378:metabolism*; D053139:Oseltamivir / Q000494:pharmacology; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014758:Viral Core Proteins / Q000378:metabolism*; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects
chemical_list: C573289:(4-(2-chloro-4-nitrophenyl)piperazin-1-yl)(1-(2-methoxyphenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methanone; D000577:Amides; D000998:Antiviral Agents; D009698:Nucleoproteins; D010879:Piperazines; D014230:Triazoles; D014758:Viral Core Proteins; D053139:Oseltamivir; D000547:Amantadine