New scaffolds of natural origin as Integrase-LEDGF/p75 interaction inhibitors: Virtual screening and activity assays

European Journal of Medicinal Chemistry

Volumn 68, Issue , 2013, Pages 405-411

  De Luca, Laura ^a   Morreale, Francesca ^a   Christ, Frauke ^b   Debyser, Zeger ^b   Ferro, Stefania ^a   Gitto, Rosaria ^a  

^a UNIVERSITY OF MESSINA   (Italy)

^b UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

HIV 1 Integrase; LEDGF p75; LEDGINs; Natural products; Protein protein interaction inhibitors; Virtual screening

Indexed keywords

2 (8 METHYL 2 OXO 4 PHENYL 2H CHROMEN 7 YLOXY) 2 PHENYL ACETIC ACID; 2 [5 (4 METHOXYBENZY LIDENE) 2,4 DITHIOXOTHIAZOLIDIN 3 YL] 3 METHYLBUTANOIC ACID; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; INTEGRASE; INTEGRASE INHIBITOR; LENS EPITHELIUM DERIVED GROWTH FACTOR; PROTEIN P75; UNCLASSIFIED DRUG;

ARTICLE; COMPETITIVE INHIBITION; CONTROLLED STUDY; CRYSTAL STRUCTURE; CYTOPATHOGENIC EFFECT; DRUG SCREENING; ENANTIOMER; HUMAN IMMUNODEFICIENCY VIRUS; HYDROGEN BOND; IN VITRO STUDY; MOLECULAR DOCKING; MOLECULAR DYNAMICS; NONHUMAN; PHARMACOPHORE; PROTEIN CONFORMATION; PROTEIN PROTEIN INTERACTION; STRUCTURE ACTIVITY RELATION;

ACQUIRED IMMUNODEFICIENCY SYNDROME; AIDS; CATALYTIC CORE DOMAIN; CCD; HIV-1; HIV-1 INTEGRASE; HUMAN IMMUNODEFICIENCY VIRUS TYPE 1; IBD; IN; INTEGRASE; INTEGRASE BINDING DOMAIN; LEDGF; LEDGF/P75; LEDGINS; LENS EPITHELIUM-DERIVED GROWTH FACTOR; MD; MM-GBSA; MOLECULAR DYNAMICS; MOLECULAR MECHANICS-GENERALIZED BORN SURFACE AREA; NATURAL PRODUCTS; NP; PDB; PPI; PROTEIN DATA BANK; PROTEIN-PROTEIN INTERACTION; PROTEIN-PROTEIN INTERACTION INHIBITORS; RMSD; ROOT MEAN SQUARE DEVIATION; VIRTUAL SCREENING; VS;

BIOLOGICAL ASSAY; BIOLOGICAL PRODUCTS; CRYSTALLOGRAPHY, X-RAY; DRUG EVALUATION, PRECLINICAL; ENZYME ACTIVATION; HIV INTEGRASE INHIBITORS; HUMANS; INTEGRASE INHIBITORS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; MODELS, MOLECULAR; MOLECULAR DOCKING SIMULATION; MOLECULAR STRUCTURE;

EID: 84883106708     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2013.07.025     Document Type: Article

References (33)

1. FDA approves Raltegravir tablets AIDS Patient Care STDS 21 2007 889
2. K. Ramkumar, E. Serrao, S. Odde, and N. Neamati HIV-1 integrase inhibitors: 2007-2008 update Med. Res. Rev. 30 2010 890 954
3. L.Q. Al-Mawsawi, and N. Neamati Allosteric inhibitor development targeting HIV-1 integrase ChemMedChem 6 2011 228 241
4. O. Taltynov, B.A. Desimmie, J. Demeulemeester, F. Christ, and Z. Debyser Cellular cofactors of lentiviral integrase: from target validation to drug discovery Mol. Biol. Int. 2012 2012 863405
5. L. De Luca, S. Ferro, F. Morreale, and A. Chimirri Inhibition of the interaction between HIV-1 integrase and its cofactor LEDGF/p75: a promising approach in anti-retroviral therapy Mini Rev. Med. Chem. 11 2011 714 727
6. L. De Luca, S. Ferro, F. Morreale, S. De Grazia, and A. Chimirri Inhibitors of the interactions between HIV-1 IN and the cofactor LEDGF/p75 ChemMedChem 6 2011 1184 1191
7. L.Q. Al-Mawsawi, and N. Neamati Blocking interactions between HIV-1 integrase and cellular cofactors: an emerging anti-retroviral strategy Trends Pharmacol. Sci. 28 2007 526 535 (Pubitemid 47488505)
8. A. Engelman, and P. Cherepanov The lentiviral integrase binding protein LEDGF/p75 and HIV-1 replication PLoS Pathog. 4 2008 e1000046
9. P. Cherepanov, A.L. Ambrosio, S. Rahman, T. Ellenberger, and A. Engelman Structural basis for the recognition between HIV-1 integrase and transcriptional coactivator p75 Proc. Natl. Acad. Sci. U S A 102 2005 17308 17313 (Pubitemid 41740862)
10. L. De Luca, S. Ferro, R. Gitto, M.L. Barreca, S. Agnello, F. Christ, Z. Debyser, and A. Chimirri Small molecules targeting the interaction between HIV-1 integrase and LEDGF/p75 cofactor Bioorg. Med. Chem. 18 2010 7515 7521
11. L. De Luca, M.L. Barreca, S. Ferro, F. Christ, N. Iraci, R. Gitto, A.M. Monforte, Z. Debyser, and A. Chimirri Pharmacophore-based discovery of small-molecule inhibitors of protein-protein interactions between HIV-1 integrase and cellular cofactor LEDGF/p75 ChemMedChem 4 2009 1311 1316
12. F. Christ, A. Voet, A. Marchand, S. Nicolet, B.A. Desimmie, D. Marchand, D. Bardiot, N.J. Van der Veken, B. Van Remoortel, S.V. Strelkov, M. De Maeyer, P. Chaltin, and Z. Debyser Rational design of small-molecule inhibitors of the LEDGF/p75-integrase interaction and HIV replication Nat. Chem. Biol. 6 2010 442 448
13. L. De Luca, S. Ferro, F. Morreale, F. Christ, Z. Debyser, A. Chimirri, and R. Gitto Fragment hopping approach directed at design of HIV IN-LEDGF/p75 interaction inhibitors J. Enzyme Inhib. Med. Chem. 2012
14. L. Du, Y. Zhao, J. Chen, L. Yang, Y. Zheng, Y. Tang, X. Shen, and H. Jiang D77, one benzoic acid derivative, functions as a novel anti-HIV-1 inhibitor targeting the interaction between integrase and cellular LEDGF/p75 Biochem. Biophys. Res. Commun. 375 2008 139 144
15. F. Christ, S. Shaw, J. Demeulemeester, B.A. Desimmie, A. Marchand, S. Butler, W. Smets, P. Chaltin, M. Westby, Z. Debyser, and C. Pickford Small-molecule inhibitors of the LEDGF/p75 binding site of integrase block HIV replication and modulate integrase multimerization Antimicrob. Agents Chemother. 56 2012 4365 4374
16. G. Hu, X. Li, X. Sun, W. Lu, G. Liu, J. Huang, X. Shen, and Y. Tang Identification of old drugs as potential inhibitors of HIV-1 integrase-human LEDGF/p75 interaction via molecular docking J. Mol. Model. 18 2012 4995 5003
17. T.S. Peat, D.I. Rhodes, N. Vandegraaff, G. Le, J.A. Smith, L.J. Clark, E.D. Jones, J.A. Coates, N. Thienthong, J. Newman, O. Dolezal, R. Mulder, J.H. Ryan, G.P. Savage, C.L. Francis, and J.J. Deadman Small molecule inhibitors of the LEDGF site of human immunodeficiency virus integrase identified by fragment screening and structure based design PLoS One 7 2012 e40147
18. L. De Luca, R. Gitto, F. Christ, S. Ferro, S. De Grazia, F. Morreale, Z. Debyser, and A. Chimirri 4-[1-(4-Fluorobenzyl)-4-hydroxy-1H-indol-3-yl]-2- hydroxy-4-oxobut-2-enoic acid as a prototype to develop dual inhibitors of HIV-1 integration process Antivir. Res. 92 2011 102 107
19. M. Tsiang, G.S. Jones, A. Niedziela-Majka, E. Kan, E.B. Lansdon, W. Huang, M. Hung, D. Samuel, N. Novikov, Y. Xu, M. Mitchell, H. Guo, K. Babaoglu, X. Liu, R. Geleziunas, and R. Sakowicz New class of HIV-1 integrase (IN) inhibitors with a dual mode of action J. Biol. Chem. 287 2012 21189 21203
20. X. Fan, F.H. Zhang, R.I. Al-Safi, L.F. Zeng, Y. Shabaik, B. Debnath, T.W. Sanchez, S. Odde, N. Neamati, and Y.Q. Long Design of HIV-1 integrase inhibitors targeting the catalytic domain as well as its interaction with LEDGF/p75: a scaffold hopping approach using salicylate and catechol groups Bioorg. Med. Chem. 19 2011 4935 4952
21. A.L. Harvey Natural products as a screening resource Curr. Opin. Chem. Biol. 11 2007 480 484 (Pubitemid 47593079)
22. P.A. Kollman, I. Massova, C. Reyes, B. Kuhn, S. Huo, L. Chong, M. Lee, T. Lee, Y. Duan, W. Wang, O. Donini, P. Cieplak, J. Srinivasan, D.A. Case, and T.E. Cheatham 3rd Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models Acc. Chem. Res. 33 2000 889 897 (Pubitemid 32056774)
23. L.Q. Al-Mawsawi, F. Christ, R. Dayam, Z. Debyser, and N. Neamati Inhibitory profile of a LEDGF/p75 peptide against HIV-1 integrase: insight into integrase-DNA complex formation and catalysis FEBS Lett. 582 2008 1425 1430
24. L. De Luca, F. Morreale, and A. Chimirri Insight into the fundamental interactions between LEDGF binding site inhibitors and integrase combining docking and molecular dynamics simulations J. Chem. Inf. Model. 52 2012 3245 3254
25. D. Luca, M.C. Marazzi, S. Mancinelli, S. Ceffa, A.M. Doro Altan, E. Buonomo, M.C. Felice Prosperi, B. Pedruzzi, A.M. Noorjehan, P. Scarcella, G. Liotta, and L. Palombi Prognostic value of virological and immunological responses after 6 months of antiretroviral treatment in adults with HIV-1 infection in Sub-Saharan Africa J. Acquir. Immune Defic. Syndr. 59 2011 236 244
26. S. Ferro, S.D. Grazia, L. De Luca, R. Gitto, C.E. Faliti, Z. Debyzer, and A. Chimirri Microwave assisted organic synthesis (MAOS) of small molecules as potential HIV-1 integrase inhibitors Molecules 16 2011 6858 6870
27. J.J. Irwin, T. Sterling, M.M. Mysinger, E.S. Bolstad, and R.G. Coleman ZINC: a free tool to discover chemistry for biology J. Chem. Inf. Model. 2012
28. G. Jones, P. Willett, R.C. Glen, A.R. Leach, and R. Taylor Development and validation of a genetic algorithm for flexible docking J. Mol. Biol. 267 1997 727 748 (Pubitemid 27170693)
29. D.A. Case, T.A. Darden, T.E. Cheatham III, C.L. Simmerling, J. Wang, R.E. Duke, R. Luo, R.C. Walker, W. Zhang, K.M. Merz, B. Roberts, B. Wang, S. Hayik, A. Roitberg, G. Seabra, I. Kolossváry, K.F. Wong, F. Paesani, J. Vanicek, J. Liu, X. Wu, S.R. Brozell, T. Steinbrecher, H. Gohlke, Q. Cai, X. Ye, J. Wang, M.-J. Hsieh, G. Cui, D.R. Roe, D.H. Mathews, M.G. Seetin, C. Sagui, V. Babin, T. Luchko, S. Gusarov, A. Kovalenko, and P.A. Kollman AMBER 11 2010 University of California San Francisco
30. Discovery Studio, versione 2.5.5, Accelrys Inc., San Diego, CA.
31. Y. Duan, C. Wu, S. Chowdhury, M.C. Lee, G. Xiong, W. Zhang, R. Yang, P. Cieplak, R. Luo, T. Lee, J. Caldwell, J. Wang, and P. Kollman A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations J.Comput. Chem. 24 2003 1999 2012
32. J. Wang, R.M. Wolf, J.W. Caldwell, P.A. Kollman, and D.A. Case Development and testing of a general amber force field J. Comput. Chem. 25 2004 1157 1174
33. R. Pauwels, J. Balzarini, M. Baba, R. Snoeck, D. Schols, P. Herdewijn, J. Desmyter, and E. De Clercq Rapid and automated tetrazolium-based colorimetric assay for the detection of anti-HIV compounds J. Virol. Methods 20 1988 309 321