Synthesis and evaluation of quinoxaline derivatives as potential influenza NS1A protein inhibitors.
You L, Cho EJ, Leavitt J, Ma LC, Montelione GT, Anslyn EV, Krug RM, Ellington A, Robertus JD.
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.