New type of anti-influenza agents based on benzo[d][1,3]dithiol core.
Khomenko TM,Zarubaev VV,Kireeva MV,Volobueva AS,Slita AV,Borisevich SS,Korchagina DV,Komarova NI,Volcho KP,Salakhutdinov NF
We synthesized a series of amides with a benzo[d][1,3]dithiol core. The chemical library of compounds was tested for their cytotoxicity and inhibiting activity against influenza virus A/California/07/09 (H1N1)pdm09 in MDCK cells. For each compound, values of CC, IC and selectivity index (SI) were determined. Compounds of this structure type were for the first time found to exhibit anti-influenza activity. The structure of an amide substituent in the tested compounds was demonstrated to have a significant effect on their activity against the H1N1 influenza virus and cytotoxicity. Compound 4d has a high selectivity index of about 30. 4d was shown to be most potent at early stages of viral cycle. In direct fusogenic assay it demonstrated dose-dependent activity against fusogenic activity of hemagglutinin of influenza virus. Based on molecular docking and regression analysis data, viral hemagglutinin was suggested as possible target for these new antiviral agents.