Development of polyphenols as HIV-1 integrase inhibitors: a summary and perspective.

Abstract:

:Raltegravir, the only drug targeting the integration step in HIV-1 life cycle, makes β-ketoenol integrase (IN) strand transfer inhibitor (STI) gain a definitive place in the treatment of HIV-1 infection. However, the emergence of viral strains resistant to β-ketoenol STI demands a continued effort toward the discovery of novel IN inhibitors interfering with HIV-1 IN in a mechanistically different manner. Polyphenols, among the most developed IN inhibitors, exhibit a different mechanism of action compared with β-ketoenol STI. Some of them exhibit strong IN inhibitory activity and anti-viral activity at nanomolar level and 1,5-DCQA has been in phase II clinical trial in China. It is undoubted that this kind of compounds are attractive candidates for future inhibitor design, as they should be effective against STI resistant viral strains and display synergistic effect when combined with the current existing STI. However, almost all reviews about IN inhibitors have been focused on β-ketoenol STI, while the thorough evolution and general structure-activity relationship (SAR) summaries of polyphenols as IN inhibitors had never been specially discussed. In this review, we provide a comprehensive report of the nearly twenty years development of polyphenols as IN inhibitors: summarizing general SAR and suggesting the orientation for further research. Compilation of such data will prove beneficial in developing a novel generation of IN inhibitors.

journal_name

Curr Med Chem

authors

Yu S,Zhao G

doi

10.2174/092986712803833236

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

5536-61

issue

32

eissn

0929-8673

issn

1875-533X

pii

CMC-EPUB-20120827-4

journal_volume

19

pub_type

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