Inhibition of in vitro and in vivo HIV replication by a distamycin analogue that interferes with chemokine receptor function: a candidate for chemotherapeutic and microbicidal application

Journal of Medicinal Chemistry
O M HowardW G Rice

Abstract

Select chemokine receptors act as coreceptors for HIV-1 entry into human cells and represent targets for antiviral therapy. In this report we describe a distamycin analogue, 2,2'-[4, 4'-[[aminocarbonyl]amino]bis[N,4'-di[pryrrole-2-carboxamide- 1, 1'-dimethyl]]-6,8-naphthalenedisulfonic acid]hexasodium salt (NSC 651016), that selectively inhibited chemokine binding to CCR5, CCR3, CCR1, and CXCR4, but not to CXCR2 or CCR2b, and blocked chemokine-induced calcium flux. Inhibition was not due to nonspecific charge interactions at the cell surface, but was based on a specific competition for the ligand receptor interaction sites since the inhibitory effect was specific for some but not all chemoattractant receptors. NSC 651016 inhibited in vitro replication of a wide range of HIV-1 isolates, as well as HIV-2 and SIV, and exhibited in vivo anti-HIV-1 activity in a murine model. In contrast, a distamycin analogue with similar structure and charge and the monomeric form of NSC 651016 demonstrated no inhibitory effects. These data demonstrate that molecules which interfere with HIV-1 entry into cells by targeting specific chemokine coreceptors can provide a viable approach to anti-HIV-1 therapy. NSC 651016 represents an attractive candid...Continue Reading

References

Jun 1, 1996·Cytokine & Growth Factor Reviews·P M Murphy
Apr 11, 1997·The Journal of Biological Chemistry·R SolariA E Proudfoot
May 13, 1997·Proceedings of the National Academy of Sciences of the United States of America·J GoslingI F Charo
Oct 23, 1997·The Journal of Experimental Medicine·D ScholsE De Clercq
Oct 23, 1997·The Journal of Experimental Medicine·T MurakamiT Nagasawa

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Citations

Mar 21, 2000·Medicinal Research Reviews·R Horuk, H P Ng
Jun 2, 2000·Biochemical and Biophysical Research Communications·N TakamuneS Shoji
Jan 13, 2001·Springer Seminars in Immunopathology·D H McDermott, P M Murphy
May 2, 2000·Drug Discovery Today·W S BlairO B Wallace
Aug 28, 2001·Drug Discovery Today·R Cortesi, C Nastruzzi
Mar 26, 2002·Nature Reviews. Immunology·Amanda E I Proudfoot
Sep 22, 2010·Chemical Communications : Chem Comm·Ayhan S DemirKerem Buran
Jun 8, 1999·Annual Review of Immunology·E A BergerJ M Farber
Dec 19, 2013·Antiviral Research·Luis Menéndez-Arias, Mar Alvarez
Aug 2, 2002·Expert Opinion on Investigational Drugs·Jim A Turpin
Oct 1, 2008·Expert Opinion on Drug Discovery·Hirokazu TamamuraNobutaka Fujii
Apr 26, 2006·Expert Opinion on Investigational Drugs·Priscilla BiswasGiuseppe Tambussi
May 3, 2007·Expert Opinion on Pharmacotherapy·Priscilla BiswasAdriano Lazzarin
Jan 24, 2003·Expert Opinion on Therapeutic Targets·Lokesh AgrawalLokesh Agrawal
Nov 23, 2005·Expert Opinion on Therapeutic Targets·Hirokazu Tamamura, Nobutaka Fujii
Apr 19, 2015·Journal of Translational Medicine·Francesca SironiPriscilla Biswas
Jun 20, 2001·Nature Reviews. Molecular Cell Biology·J P Moore, M Stevenson
Jul 18, 2001·The Journal of General Virology·T Dragic
Dec 31, 2019·PloS One·Clayton K CollingsJohn N Anderson
Jan 22, 2010·Organic & Biomolecular Chemistry·Tetsuo NarumiNobutaka Fujii
Feb 12, 2011·ChemMedChem·Tomohiro TanakaHirokazu Tamamura
Feb 16, 2012·Bioorganicheskaia khimiia·E O BaranovaV I Shvets
Jan 1, 2008·Perspectives in Medicinal Chemistry·Hirokazu TamamuraNobutaka Fujii
Jan 27, 1999·Biochemical and Biophysical Research Communications·H TamamuraN Fujii
Sep 11, 2003·Chemical Reviews·Zhongli Gao, William A Metz

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