4KIL

7-(4-fluorophenyl)-3-hydroxyquinolin-2(1H)-one bound to influenza 2009 H1N1 endonuclease

Summary for 4KIL

• Entry DOI: 10.2210/pdb4kil/pdb
• Descriptor: Polymerase PA, MANGANESE (II) ION, SULFATE ION, ... (6 entities in total)
• Functional Keywords: endonuclease, cap-snatching, influenza, rna binding protein-inhibitor complex, rna binding protein/inhibitor
• Biological source: Influenza A virus (A/Lima/WRAIR1695P/2009(H1N1))
• Total number of polymer chains: 1
• Total formula weight: 25438.52

Authors

Bauman, J.D.,Patel, D.,Das, K.,Arnold, E. (deposition date: 2013-05-02, release date: 2013-05-29, Last modification date: 2024-02-28)

Primary citation

Sagong, H.Y.,Parhi, A.,Bauman, J.D.,Patel, D.,Vijayan, R.S.,Das, K.,Arnold, E.,LaVoie, E.J.
3-Hydroxyquinolin-2(1H)-ones As Inhibitors of Influenza A Endonuclease.
ACS Med Chem Lett, 4:547-550, 2013

PubMed Abstract: 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.

PubMed: 24936242
DOI: 10.1021/ml4001112

Experimental method

X-RAY DIFFRACTION (1.75 Å)