当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Discovery of inhibitors to block interactions of HIV-1 integrase with human LEDGF/p75 via structure-based virtual screening and bioassays.

Discovery of inhibitors to block interactions of HIV-1 integrase with human LEDGF/p75 via structure-based virtual screening and bioassays.

Abstract：

:This study aims to identify inhibitors that bind at the interface of HIV-1 integrase (IN) and human LEDGF/p75, which represents a novel target for anti-HIV therapy. To date, only a few such inhibitors have been reported. Here structure-based virtual screening was performed to search for the inhibitors from an in-house library of natural products and their derivatives. Among the 38 compounds selected by our strategy, 18 hits were discovered. The two most potent inhibitors showed IC(50) values at 0.32 and 0.26 μM, respectively. Three compounds were subsequently selected for anti-HIV assays, among which (E)-3-(2-chlorophenyl)-1-(2,4-dihydroxyphenyl)prop-2-en-1-one (NPD170) showed the highest antiviral activity (EC(50) = 1.81 μM). The antiviral mechanism of these compounds was further explored, and the results validated that the compounds interrupted the binding of transfected IN to endogenous LEDGF/p75. These findings could be helpful for anti-HIV drug discovery.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Hu G,Li X,Zhang X,Li Y,Ma L,Yang LM,Liu G,Li W,Huang J,Shen X,Hu L,Zheng YT,Tang Y

doi

10.1021/jm301226a

subject

Has Abstract

pub_date

2012-11-26 00:00:00

pages

10108-17

issue

22

eissn

0022-2623

issn

1520-4804

journal_volume

55

pub_type

杂志文章

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