title: Exploring naphthyl-carbohydrazides as inhibitors of influenza A viruses.
abstract: A library of hydrazide derivatives was synthesized to target non-structural protein 1 of influenza A virus (NS1) as a means to develop anti-influenza drug leads. The lead compound 3-hydroxy-N-[(Z)-1-(5,6,7,8-tetrahydronaphthalen-2-yl)ethylideneamino]naphthalene-2-carboxamide, which we denoted as "HENC", was identified by its ability to increase the melting temperature of the effector domain (ED) of the NS1 protein, as assayed using differential scanning fluorimetry. A library of HENC analogs was tested for inhibitory effect against influenza A virus replication in MDCK cells. A systematic diversification of HENC revealed the identity of the R group attached to the imine carbon atom significantly influenced the antiviral activity. A phenyl or cyclohexyl at this position yielded the most potent antiviral activity. The phenyl containing compound had antiviral activity similar to that of the active form of oseltamivir (Tamiflu), and had no detectable effect on cell viability.
authors.affiliation: Department of Chemistry, University of Texas at Austin, Austin, TX 78712, USA; Molecular Genetics and Microbiology, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Sanmitra
authors.initials: S
authors.lastname: Barman
authors.affiliation: Department of Chemistry, University of Texas at Austin, Austin, TX 78712, USA; Molecular Genetics and Microbiology, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: You
authors.affiliation: Department of Chemistry, University of Texas at Austin, Austin, TX 78712, USA; Molecular Genetics and Microbiology, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Ran
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Chemistry, University of Texas at Austin, Austin, TX 78712, USA; Molecular Genetics and Microbiology, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Vlad
authors.initials: V
authors.lastname: Codrea
authors.affiliation: Department of Chemistry, University of Texas at Austin, Austin, TX 78712, USA; Molecular Genetics and Microbiology, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Kago
authors.affiliation: Department of Chemistry, University of Texas at Austin, Austin, TX 78712, USA; Molecular Genetics and Microbiology, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Edupuganti
authors.affiliation: Department of Chemistry, University of Texas at Austin, Austin, TX 78712, USA; Molecular Genetics and Microbiology, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Jon
authors.initials: J
authors.lastname: Robertus
authors.affiliation: Molecular Genetics and Microbiology, University of Texas at Austin, Austin, TX 78712, USA. Electronic address: rkrug@austin.utexas.edu.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Krug
authors.affiliation: Department of Chemistry, University of Texas at Austin, Austin, TX 78712, USA. Electronic address: anslyn@austin.utexas.edu.
authors.forename: Eric V
authors.initials: EV
authors.lastname: Anslyn
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D006834:Hydrazines / Q000737:chemistry* / Q000494:pharmacology*; D009980:Influenza A virus / Q000187:drug effects* / Q000502:physiology; D009976:Orthomyxoviridae Infections / Q000188:drug therapy; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D006834:Hydrazines; C085820:INS1 protein, influenza virus; D017361:Viral Nonstructural Proteins; C019289:carbohydrazide
keywords: Carbohydrazide; Hemagglutinin; Influenza; Plaque; Real time PCR