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3‑Hydroxyquinolin-2(1H)‑ones As Inhibitors of Influenza A Endonuclease

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journal contribution
posted on 13.06.2013, 00:00 authored by Hye Yeon Sagong, Ajit Parhi, Joseph D. Bauman, Disha Patel, R. S. K. Vijayan, Kalyan Das, Eddy Arnold, Edmond J. LaVoie
Several 3-hydroxyquinolin-2­(1H)-ones derivatives were synthesized and evaluated as inhibitors of 2009 pandemic H1N1 influenza A endonuclease. All five of the monobrominated 3-hydroxyquinolin­(1H)-2-ones derivatives were synthesized. Suzuki-coupling of p-fluorophenylboronic acid with each of these brominated derivatives provided the respective p-fluorophenyl 3-hydroxyquinolin­(1H)-2-ones. In addition to 3-hydroxyquinolin-2­(1H)-one, its 4-methyl, 4-phenyl, 4-methyl-7-(p-fluorophenyl), and 4-phenyl-7-(p-fluorophenyl) derivatives were also synthesized. Comparative studies on their relative activity revealed that both 6- and 7-(p-fluorophenyl)-3-hydroxyquinolin-2­(1H)-one are among the more potent inhibitors of H1N1 influenza A endonuclease. An X-ray crystal structure of 7-(p-fluorophenyl)-3-hydroxyquinolin-2­(1H)-one complexed to the influenza endonuclease revealed that this molecule chelates to two metal ions at the active site of the enzyme.

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