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Molecules 2015, 20(4), 6978-6999;

Discovery of Metal Ions Chelator Quercetin Derivatives with Potent Anti-HCV Activities

Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhang-Heng Rd, Shanghai 201203, China
Institute of Pharmacy, HamHung Pharmaceutical University, HamHung 999093, Democratic People's Republic of Korea
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 3 March 2015 / Revised: 8 April 2015 / Accepted: 13 April 2015 / Published: 16 April 2015
(This article belongs to the Section Medicinal Chemistry)
Full-Text   |   PDF [780 KB, uploaded 16 April 2015]   |  


Analogues or isosteres of α,γ-diketoacid (DKA) 1a show potent inhibition of hepatitis C virus (HCV) NS5B polymerase through chelation of the two magnesium ions at the active site. The anti-HCV activity of the flavonoid quercetin (2) could partly be attributed to it being a structural mimic of DKAs. In order to delineate the structural features required for the inhibitory effect and improve the anti-HCV potency, two novel types of quercetin analogues, 7-O-arylmethylquercetins and quercetin-3-O-benzoic acid esters, were designed, synthesized and evaluated for their anti-HCV properties in cell-based assays. Among the 38 newly synthesized compounds, 7-O-substituted derivative 3i and 3-O-substituted derivative 4f were found to be the most active in the corresponding series (EC50 = 3.8 μM and 9.0 μΜ, respectively). Docking studies suggested that the quercetin analogues are capable of establishing key coordination with the two magnesium ions as well as interactions with residues at the active site of HCV NS5B. View Full-Text
Keywords: anti-HCV activities; diketoacids mimic; quercetin derivatives; synthesis; docking anti-HCV activities; diketoacids mimic; quercetin derivatives; synthesis; docking

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Zhong, D.; Liu, M.; Cao, Y.; Zhu, Y.; Bian, S.; Zhou, J.; Wu, F.; Ryu, K.-C.; Zhou, L.; Ye, D. Discovery of Metal Ions Chelator Quercetin Derivatives with Potent Anti-HCV Activities. Molecules 2015, 20, 6978-6999.

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