Inhibition of HIV-1 integrase by flavones, caffeic acid phenethyl ester (CAPE) and related compounds

Biochemical Pharmacology
M R FesenK W Kohn

Abstract

The inhibition of HIV-1 integrase by flavones and related compounds was investigated biochemically and by means of structure-activity relationships. Purified enzyme and synthetic oligonucleotides were used to assay for three reactions catalysed by integrase: (1) processing of 3' termini by cleavage of the terminal dinucleotide; (2) strand transfer, which models the integration step; and (3) "disintegration," which models the reversal of the strand transfer reaction. Inhibitions of all three reactions by flavones generally occurred in parallel, but caffeic acid phenethyl ester (CAPE) appeared to inhibit reaction 2 selectively. CAPE, however, inhibited reactions 1 and 3 effectively when preincubated with the enzyme, suggesting that this compound differs from the flavones primarily in requiring more time to block the enzyme. The core integrase fragment consisting of amino acids 50-212 retained the ability to catalyse reaction 3, and flavones and CAPE retained the ability to inhibit. Hence, the putative zinc-finger region that is deleted in this fragment is probably not the target of inhibition. Inhibition by flavones usually required the presence of at least one ortho pair of phenolic hydroxyl groups and at least one or two additi...Continue Reading

References

Aug 1, 1992·Molecular and Cellular Biology·N HosokawaK Nagata
Jul 31, 1992·Biochemical and Biophysical Research Communications·W F MatterC J Vlahos
Oct 20, 1992·Biochemical Pharmacology·A J ElliottR S Pardini
Jan 1, 1992·Annual Review of Genetics·S P Goff
Jul 31, 1992·Biochemical and Biophysical Research Communications·Y J LeeP M Corry
Apr 1, 1991·Biochemical Medicine and Metabolic Biology·T S TeoN P Das
Jan 1, 1990·Free Radical Biology & Medicine·A T CanadaR P Mason
May 25, 1991·Nucleic Acids Research·R CraigieA Engelman
Jul 15, 1990·Biochemical Pharmacology·U R KuppusamyN P Das
Jul 1, 1989·European Journal of Drug Metabolism and Pharmacokinetics·M H SiessE Gaydou
May 28, 1993·Science·M I Johnston, D F Hoth
Jan 1, 1993·The Biochemical Journal·F ShibasakiT Takenawa
Jan 7, 1993·Biochemical Pharmacology·T NakayamaS Kawakishi
Mar 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·M R FesenY Pommier
Apr 1, 1993·Archives of Biochemistry and Biophysics·S ChenP S Deng

❮ Previous
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Citations

May 3, 2002·Reviews in Medical Virology·Vasu Nair
Nov 5, 1999·Archives of Pharmacal Research·H K KimH Huh
Sep 21, 2005·Cancer Chemotherapy and Pharmacology·Yi-Hsien LinSang-Hue Yen
May 13, 2008·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Yi-Yen LeeTai-Tong Wong
Apr 18, 1995·Biochemical Pharmacology·A MazumderY Pommier
Dec 4, 2003·European Journal of Medicinal Chemistry·Jaime SouzaAlbérico Borges Ferreira da Silva
Nov 21, 2002·Journal of Molecular Biology·V R de SoultraitM L Andréola
Sep 7, 2000·Antiviral Research·Y PommierN Neamati
Feb 26, 1998·Antiviral Research·E Asante-Appiah, A M Skalka
May 23, 2001·Pathologie-biologie·J d'AngeloH Leh
Aug 15, 2002·Current Biology : CB·Christophe PannecouqueZeger Debyser
Feb 24, 2001·Bioorganic & Medicinal Chemistry·B EtzenhouserC D Selassie
Sep 6, 2002·Bioorganic & Medicinal Chemistry·David C RowleyWilliam Fenical
Feb 25, 2005·Nature Reviews. Drug Discovery·Yves PommierChristophe Marchand
Dec 5, 1995·Proceedings of the National Academy of Sciences of the United States of America·R A Puras LutzkeR H Plasterk
Jun 25, 1996·Proceedings of the National Academy of Sciences of the United States of America·W E RobinsonS A Chow
Sep 3, 1996·Proceedings of the National Academy of Sciences of the United States of America·C M FarnetF D Bushman
Feb 2, 2012·Journal of Biomolecular Structure & Dynamics·Miriam SgobbaShozeb Haider
Jan 25, 2006·Critical Reviews in Food Science and Nutrition·Sailendra N NichenametlaJerry H Exon
Mar 28, 1998·SAR and QSAR in Environmental Research·G W MilneS Wang
Jan 1, 1996·AIDS Research and Human Retroviruses·J W CritchfieldT M Folks
Jan 29, 2013·Foodborne Pathogens and Disease·Moises Navarro-NavarroCarlos Velazquez
Dec 19, 2008·Retrovirology·Olivier DelelisJean-François Mouscadet
Dec 6, 2005·Biological & Pharmaceutical Bulletin·Mayuko UjibeMasaaki Ishikawa
Dec 25, 2002·Chemical & Pharmaceutical Bulletin·Pili Chih-Min MaoLing-Yih Hsu
Dec 7, 2007·Chemical & Pharmaceutical Bulletin·Chih-Chia ChiangLing-Yih Hsu
Jul 28, 2013·International Journal of Molecular Sciences·Jung-Chun LiaoYueh-Hsiung Kuo
Aug 5, 2014·Chemical & Pharmaceutical Bulletin·Wipa TupchiangmaiYongsak Sritana-anant
Oct 15, 2014·Journal of Molecular Modeling·Houria DjeradiAbdelkrim Cheriti
Mar 12, 2010·Journal of Cancer Research and Clinical Oncology·Cığır Biray AvcıGüray Saydam
May 16, 2012·Journal of Virological Methods·Ying-Shan HanMark A Wainberg

❮ Previous
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