title: Synthesis and evaluation of quinoxaline derivatives as potential influenza NS1A protein inhibitors.
abstract: A library of quinoxaline derivatives were prepared to target non-structural protein 1 of influenza A (NS1A) as a means to develop anti-influenza drug leads. An in vitro fluorescence polarization assay demonstrated that these compounds disrupted the dsRNA-NS1A interaction to varying extents. Changes of substituent at positions 2, 3 and 6 on the quinoxaline ring led to variance in responses. The most active compounds (35 and 44) had IC(50) values in the range of low micromolar concentration without exhibiting significant dsRNA intercalation. Compound 44 was able to inhibit influenza A/Udorn/72 virus growth.
authors.affiliation: Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: You
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Cho
authors.forename: John
authors.initials: J
authors.lastname: Leavitt
authors.forename: Li-Chung
authors.initials: LC
authors.lastname: Ma
authors.forename: Gaetano T
authors.initials: GT
authors.lastname: Montelione
authors.forename: Eric V
authors.initials: EV
authors.lastname: Anslyn
authors.forename: Robert M
authors.initials: RM
authors.lastname: Krug
authors.forename: Andrew
authors.initials: A
authors.lastname: Ellington
authors.forename: Jon D
authors.initials: JD
authors.lastname: Robertus
mesh_terms: D004789:Enzyme Activation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors*; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016601:RNA-Binding Proteins; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000037:antagonists & inhibitors*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; C114207:IVNS1ABP protein, human; D009687:Nuclear Proteins; D011810:Quinoxalines; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D017361:Viral Nonstructural Proteins