A 1,8-naphthyridone derivative targets the HIV-1 Tat-mediated transcription and potently inhibits the HIV-1 replication

Journal of Medicinal Chemistry

Volumn 53, Issue 2, 2010, Pages 641-648

  Massari, Serena ^a   Daelemans, Dirk ^b   Barreca, Maria Letizia ^a   Knezevich, Anna ^c   Sabatini, Stefano ^a   Cecchetti, Violetta ^a   Marcello, Alessandro ^c   Pannecouque, Christophe ^b   Tabarrini, Oriana ^a  

^a UNIVERSITY OF PERUGIA   (Italy)

^b REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

^c INTERNATIONAL CENTRE FOR GENETIC ENGINEERING AND BIOTECHNOLOGY   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

1 METHYL 4 OXO 7 (4 PYRIDIN 2 YLPIPERAZIN 1 YL) 1,4 DIHYDRO 1,8 NAPHTHYRIDINE 3 CARBOXYLIC ACID; 1 METHYL 4 OXO 7 [4 (1,3 THIAZOL 2 YL)PIPERAZIN 1 YL] 1,4 DIHYDRO 1,8 NAPHTHYRIDINE 3 CARBOXYLIC ACID; 1 METHYL 4 OXO 7 [4 [3 (TRIFLUOROMETHYL)PHENYL]PIPERAZIN 1 YL] 1,4 DIHYDRO 1,8 NAPHTHYRIDINE 3 CARBOXYLIC ACID; 1,8 NAPHTHYRIDONE DERIVATIVE; 7 [4 (1,3 BENZOTHIAZOL 2 YL)PIPERAZIN 1 YL] 1 METHYL 4 OXO 1,4 DIHYDRO 1,8 NAPHTHYRIDINE 3 CARBOXYLIC ACID; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; CYCLIN DEPENDENT KINASE 9; GLUTATHIONE TRANSFERASE; HISTONE ACETYLTRANSFERASE; INTEGRASE; N (4 FLUOROBENZYL) 8 HYDROXY 5 (TETRAHYDRO 2H 1,2 THIAZIN 2 YL) 1,6 NAPHTHYRIDINE 7 CARBOXAMIDE S,S DIOXIDE; NEVIRAPINE; PHORBOL 13 ACETATE 12 MYRISTATE; RECOMBINANT ENZYME; RITONAVIR; TRANSACTIVATOR PROTEIN; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; VIRUS DNA; ZIDOVUDINE;

ANTIVIRAL ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG MECHANISM; DRUG POTENCY; DRUG SOLUBILITY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ASSAY; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; LONG TERMINAL REPEAT; NONHUMAN; PERIPHERAL BLOOD MONONUCLEAR CELL; TRANSACTIVATION; VIRUS INHIBITION; VIRUS MUTATION; VIRUS REPLICATION; VIRUS RESISTANCE;

ANTI-HIV AGENTS; CELL LINE; DRUG DELIVERY SYSTEMS; DRUG RESISTANCE, VIRAL; HIV INFECTIONS; HIV-1; HIV-2; HUMANS; NAPHTHYRIDINES; TAT GENE PRODUCTS, HUMAN IMMUNODEFICIENCY VIRUS; TRANSCRIPTION, GENETIC; VIRUS REPLICATION;

EID: 77249177585     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm901211d     Document Type: Article

References (41)

1. Fätkenheuer, G.; Pozniak, A. L.; Johnson, M. A.; Plettenberg, A.; Staszewski, S.; Hoepelman, A. I.; Saag, M. S.; Goebel, F. D.; Rockstroh, J. K.; Dezube, B. J.; Jenkins, T. M.; Medhurst, C.; Sullivan, J. F.; Ridgway, C.; Abel, S.; James, I. T.; Youle, M.; van der Ryst, E. Efficacy of Short-Term Monotherapy with Maraviroc, a New CCR5 Antagonist, in Patients Infected with HIV-1. Nat. Med. 2005, 11, 1170-1172.
2. Grinsztejn, B.; Nguyen, B. Y.; Katlama, C.; Gatell, J. M.; Lazzarin, A.; Vittecoq, D.; Gonzalez, C. J.; Chen, J.; Harvey, C. M.; Isaacs, R. D. Safety and Efficacy of the HIV-1 Integrase Inhibitor Raltegravir (MK-0518) in Treatment-Experienced Patients with Multidrug-Resistant Virus: a Phase II Randomised Controlled Trial. Lancet 2007, 369, 1261-1269.
3. Marcello, A. Latency: The Hidden HIV-1 Challenge. Retrovirology 2006, 3, 1-7.
4. Cecchetti, V.; Parolin, C.; Moro, S.; Pecere, T.; Filipponi, E.; Calistri, A.; Tabarrini, O.; Gatto, B.; Palumbo, M.; Fravolini, A.; Palù, G. 6-Aminoquinolones as New Potential Anti-HIV Agents. J. Med. Chem. 2000, 43, 3799-3802.
5. Tabarrini, O.; Stevens, M.; Checchetti, V.; Sabatini, S.; Dell'Uomo, M.; Manfroni, G.; Palumbo, M.; Pannecouque, C.; De Clercq, E.; Fravolini, A. Structure Modification of 6-Aminoquinolones with Potent Anti-HIV Activity. J. Med. Chem. 2004, 47, 5567-5578.
6. Tabarrini, O.; Massari, S.; Daelemans, D.; Stevens, M.; Manfroni, G.; Sabatini, S.; Balzarini, J.; Cecchetti, V.; Pannecouque, C.; Fravolini, A. Structure - Activity Relationship Study on Anti-HIV 6-Desfluoroquinolones. J. Med. Chem. 2008, 51, 5454-5458.
7. Massari, S.; Daelemans, D.; Manfroni, G.; Sabatini, S.; Tabarrini, O.; Pannecouque, C.; Cecchetti, V. Studies on Anti-HIV Quinolones: New Insights on the C-6 Position. Bioorg. Med. Chem. 2009, 17, 667-674.
8. Stevens, M.; Balzarini, J.; Tabarrini, O.; Andrei, G.; Snoeck, R.; Cecchetti, V.; Fravolini, A.; De Clercq, E.; Pannecouque, C. Cell-Dependent Interference of a Series of New 6-Aminoquinolone Derivatives with Viral (HIV/CMV) Transactivation. J. Antimicrob. Chemother. 2005, 56, 847-855.
9. Stevens, M.; De Clercq, E.; Balzarini, J. The Regulation of HIV-1 Transcription: Molecular Targets for Chemotherapeutic Intervention. Med. Res. Rev. 2006, 26, 595-625.
10. Baba, M. Recent Status of HIV-1 Gene Expression Inhibitors. Antivir. Res. 2006, 71, 301-306.
11. Richter, S. N.; Palù, G. Inhibitors of HIV-1 Tat-Mediated Transactivation. Curr. Med. Chem. 2006, 13, 1305-1315.
12. Baba, M. Inhibitors of HIV-1 Gene Expression and Transcription. Curr. Top. Med. Chem. 2004, 4, 871-883.
13. Yang, M. Discovery of Tat-TAR Interaction Inhibitors for HIV-1. Curr. Drug Targets: Infect. Disord. 2005, 5, 433-444.
14. Rusnati, M; Presta, M. HIV-1 Tat Protein: A Target for the Development of Anti-AIDS Therapies. Drugs Fut. 2002, 27, 481-493.
15. Stevens, M.; Pollicita, M.; Pannecouque, C.; Verbeken, E.; Tabarrini, O.; Cecchetti, V.; Acquaro, S.; Perno, C. F.; Fravolini, A.; Schols, D.; De Clercq, E; Balzarini, J. A Novel in Vivo Model for the Study of HIV-1 Transcription Inhibitors: Evaluation of New 6-Desfluoroquinolone Derivatives (6-DFQs). Antimicrob. Agents Chemother. 2007, 4, 1407-1413.
16. Anderson, D.; Beutel, B.; Bosse, T. D.; Clark, R.; Cooper, C.; Dandliker, P.; David, C.; Yu-Gui, H.; Todd, M.; Hinman, M.; Kalvin, D.; Larson, D. P.; Lynch, L.; Ma, Z.; Motter, C.; Palazzo, F.; Rosenberg, T.; Rehm, T.; Sanders, W.; Tufano, M.; Wagner, R.; Weitzberg, M.; Yong, H.; Zhang, T. Preparation of Naphthyridines as Antibacterial Compounds. U.S. Patent US 2003232818, 2003.
17. Daelemans, D.; Pannecouque, C.; Pavlakis, G. N.; Tabarrini, O.; De Clercq, E. A Novel and Efficient Approach to Discriminate Between Pre- and Post-Transcription HIV Inhibitors. Mol. Pharmacol. 2005, 67, 1574-1580.
18. Stevens, M.; Balzarini, J.; Lagoja, I. M.; Noppen, B.; Franc-ois, K.; Van Aerschot, A.; Herdewijn, P.; De Clercq, E.; Pannecouque, C. Inhibition of Human Immunodeficiency Virus Type 1 Transcription by N-Aminoimidazole Derivatives. Virology 2007, 365, 220-237.
19. Nair, V.; Chi, G.HIV Integrase Inhibitors as Therapeutic Agents in AIDS. Rev. Med. Virol. 2007, 17, 277-295.
20. Sato, M.; Motomura, T.; Aramaki, H.; Matsuda, T.; Yamashita, M.; Ito, Y.; Kawakami, H.; Matsuzaki, Y.; Watanabe, W.; Yamataka, K.; Ikeda, S.; Kodama, E.; Matsuoka, M.; Shinkai, H. Novel HIV-1 Integrase Inhibitors Derived from Quinolone Antibiotics. J. Med. Chem. 2006, 49, 1506-1508.
21. Daelemans, D.; Lu, R.; De Clercq, E.; Engelman, A. Characterization of a Replication-Competent, Integrase-Defective Human Immunodeficiency Virus (HIV)/Simian Virus 40 Chimera as a Powerful Tool for the Discovery and Validation of HIV Integrase Inhibitors. J. Virol. 2007, 81, 4381-4385.
22. Hazuda, D. J.; Anthony, N. J.; Gomez, R. P.; Jolly, S. M.; Wai, J. S.; Zhuang, L.; Fisher, T. E.; Embrey, M.; Guare, J. P., Jr.; Egbertson, M. S.; Vacca, J. P.; Huff, J. R.; Felock, P. J.; Witmer, M. V.; Stillmock, K. A.; Danovich, R.; Grobler, J.; Miller, M. D.; Espeseth, A. S.; Jin, L.; Chen, I. W.; Lin, J. H.; Kassahun, K.; Ellis, J. D.; Wong, B. K.; Xu, W.; Pearson, P. G.; Schleif, W. A.; Cortese, R.; Emini, E.; Summa, V.; Holloway, M. K.; Young, S. D. A Naphthyridine Carboxamide Provides Evidence for Discordant Resistance Between Mechanistically Identical Inhibitors of HIV-1 Integrase. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 11233-11238.
23. Barreca, M. L.; Iraci, N.; De Luca, L.; Chimirri, A. Induced-fit Docking Approach Provides Insight into the Binding Mode and Mechanism of Action of HIV-1 Integrase Inhibitors (pNA). ChemMedChem 2009, 4, 1446-1456.
24. Richter, S.; Parolin, C.; Gatto, B.; Del Vecchio, C.; Brocca-Cofano, E.; Fravolini, A.; Palu, G.; Palumbo, M. Inhibition of Human Immunodeficiency Virus Type 1 Tat-trans-Activation-Responsive Region Interaction by an Antiviral Quinolone Derivative. Antimicrob. Agents Chemother. 2004, 48, 1895-1899.
25. Richter, S.; Gatto, B.; Tabarrini, O.; Fravolini, A.; Palumbo, M. Antiviral 6-Aminoquinolones: Molecular Basis for Potency and Selectivity. Bioorg. Med. Chem. Lett. 2005, 15, 4247-4251.
26. Marcello, A.; Zoppé, M.; Giacca, M. Multiple Modes of Transcriptional Regulation by the HIV-1 Tat Transactivator. IUBMB Life 2001, 51, 175-181.
27. Verderame, M. 1,4-Disubstituted Piperazines. 3. Piperazinylbenzothiazoles. J. Med. Chem. 1972, 15, 693-694.
28. Kimura, T.; Katsube, T. Preparation of Aminoquinolone Derivatives as Anti-HIV Agents. Patent EP 572259 A1, 1994.
29. Pauwels, R.; Balzarini, J.; Baba, M.; Snoeck, R.; Schols, D.; Herdewijn, P.; Desmyter, J.; De Clercq, E. Rapid and Automated Tetrazolium-Based Colorimetric Assay for the Detection of Anti-HIV Compounds. J. Virol. Methods 1988, 20, 309-321.
30. Pannecouque, C.; Daelemans, D.; De Clercq, E. Tetrazolium-Based Colorimetric Assay for the Detection of HIV Replication Inhibitors: Revisited 20 Years Later. Nat. Protoc. 2008, 3, 427-434.
31. Popovic, M.; Sarngadharan, M. G.; Read, E.; Gallo, R. C. Detection, Isolation and Continuous Production of Cytophatic Retroviruses (HTLV-III) from Patient with AIDS and Pre-AIDS. Science 1984, 224, 497-500.
32. Barrè-Sinoussi, F.; Chermann, J. C.; Rey, F.; Nugeyre, M. T.; Chamaret, S.; Grest, J.; Dauget, C.; Axler-Blin, C.; Vezinet-Brun, F.; Rouzioux, C.; Rozenbaum, W.; Montagnier, L. Isolation of a T-Lymphotropic Retrovirus From Patient at Risk for AIDS. Science 1983, 220, 868-871.
33. Miyoshi, I.; Taguchi, H.; Kobonishi, I.; Yoshimoto, S.; Ohtsuki, Y.; Shiraishi, Y.; Akagi, T.; Type, C Virus-Producing Cell Lines Derived from Adult T Cell Leukaemia. Gann. Monogr. 1982, 28, 219-228.
34. Japour, A. J.; Mayers, D. L.; Johnson, V. A.; Kuritzkes, D. R.; Beckett, L. A.; Arduino, J. M.; Lane, J.; Black, R. L.; Reichelderfer, P. S.; D'Aquila, R. T.; Crumpacker, C. S. Standardized Peripheral Blood Mononuclear Cell Culture Assay for Determination of Drug Susceptibilities of Clinical Human Immunodeficiency Virus Type 1 Isolates. Antimicrob. Agents Chemother. 1993, 37, 1095-1101.
35. Jordan, A.; Bisgrove, D.; Verdin, E. HIV Reproducibly Establishes a Latent Infection after Acute Infection of T Cells in Vitro. EMBO J. 2003, 22, 1868-1877.
36. Pauwels, R.; Andries, K.; Desmyter, J.; Schols, D.; Kukla, M. J.; Breslin, H. J.; Raymaeckers, A.; Van Gelder, J.; Woestenborghs, R.; Heykants, J. Potent and Selective Inhibition of HIV-1 Replication by a Novel Series of TIBO Derivatives. Nature 1990, 343, 470-474.
37. du Chéné, I.; Basyuk, E.; Lin, Y. L.; Triboulet, R.; Knezevich, A.; Chable-Bessia, C.; Mettling, C.; Baillat, V.; Reynes, J.; Corbeau, P.; Bertrand, E.; Marcello, A.; Emiliani, S.; Kiernan, R.; Benkirane, M. Suv39H1 and HP1gamma are Responsible for Chromatin-Mediated HIV-1 Transcriptional Silencing and Post-Integration Latency. EMBO J. 2007, 26, 424-435.
38. Sabò, A.; Lusic, M.; Cereseto, A.; Giacca, M. Acetylation of Conserved Lysines in the Catalytic Core of Cyclin-Dependent Kinase 9 Inhibits Kinase Activity and Regulates Transcription. Mol. Cell. Biol. 2008, 28, 2201-2212.
39. Pantano, S.; Marcello, A.; Ferrari, A.; Gaudiosi, D.; Sabò, A.; Pellegrini, V.; Beltram, F.; Giacca, M.; Carloni, P. Insights on HIV-1 Tat:P/CAF Bromodomain Molecular Recognition from In Vivo Experiments and Molecular-Dynamics Simulations. Proteins: Struct., Funct., Bioinf. 2006, 62, 1062-1073.
40. Marzio, G.; Wagener, C.; Gutierrez, M. I.; Cartwright, P.; Helin, K.; Giacca, M. E2F Family Members are Differentially Regulated by Reversible Acetylation. J. Biol. Chem. 2000, 275, 10887-10892.
41. DeLano, W. L. The PyMOL Molecular Graphics System (2002) on World Wide Web http://www.pymol.org.