Docking and 3-D QSAR studies on indolyl aryl sulfones. Binding mode exploration at the HIV-1 reverse transcriptase non-nucleoside binding site and design of highly active N-(2-hydroxyethyl) carboxamide and N-(2-hydroxyethyl) carbohydrazide derivatives

Journal of Medicinal Chemistry

Volumn 48, Issue 1, 2005, Pages 213-223

  Ragno, Rino ^a   Artico, Marino ^a   De Martino, Gabriella ^a   La Regina, Giuseppe ^a   Coluccia, Antonio ^a   Di Pasquali, Alessandra ^a   Silvestri, Romano ^a  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

N (2 HYDROXYETHYL) 3 (PHENYLTHIO) 5 CHLORO 1H INDOLE 2 CARBOXAMIDE; N (2 HYDROXYETHYL) 3 [(2,4 DIMETHYLPHENYL)SULFONYL] 5 CHLORO 1H INDOLE 2 CARBOXAMIDE; N (2 HYDROXYETHYL) 3 [(3,5 DIMETHYLPHENYL)SULFONYL] 5 CHLORO 1H INDOLE 2 CARBOXAMIDE; N (2 HYDROXYETHYL)CARBOHYDRAZIDE DERIVATIVE; N (2 HYDROXYETHYL)CARBOXAMIDE DERIVATIVE; N' (2 HYDROXYETHYL) 3 [(2,4 DIMETHYLPHENYL)THIO] 5 CHLORO 1H INDOLE 2 CARBOHYDRAZIDE; N' (2 HYDROXYETHYL) 3 [(3 METHYLPHENYL)SULFONYL] 5 CHLORO 1H INDOLE 2 CARBOHYDRAZIDE; N' (2 HYDROXYETHYL) 3 [(3,5 DIMETHYLPHENYL)SULFONYL] 5 CHLORO 1H INDOLE 2 CARBOHYDRAZIDE; RNA DIRECTED DNA POLYMERASE; RNA DIRECTED DNA POLYMERASE INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; BINDING SITE; DRUG BINDING; DRUG DESIGN; DRUG STRUCTURE; DRUG SYNTHESIS; MOLECULAR INTERACTION; MOLECULAR MODEL; QUANTITATIVE STRUCTURE ACTIVITY RELATION; THREE DIMENSIONAL IMAGING;

BINDING SITES; CELLS, CULTURED; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; HIV-1 REVERSE TRANSCRIPTASE; HUMANS; HYDRAZINES; MICROBIAL SENSITIVITY TESTS; MODELS, MOLECULAR; NUCLEOSIDES; PROTEIN CONFORMATION; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; REVERSE TRANSCRIPTASE INHIBITORS; SOFTWARE; SULFONES;

EID: 12144279076     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm040854k     Document Type: Article

References (45)

1. WHO/UNAIDS AIDS Epidemic Update. December 2003.
2. Williams, I. G. Enfuvirtide (Fuzeon): The first fusion inhibitor. Int. J. Clin. Pract. 2003, 57, 890-897.
3. Vandamme, A. M.; Van Vaerenbergh, K.; De Clercq, E. Anti-human immunodeficiency virus drug combination strategies. Antivir. Chem. Chemoth. 1998, 9, 187-203.
4. Condra, J. H.; Miller, M. D.; Hazuda, D. J.; Emini, E. A. Potential new therapies for the treatment of HIV-1 infection. Annu. Rev. Med. 2002, 53, 541-555.
5. Young, S. D. Recent advances in the chemotherapy of HIV. Annu. Rep. Med. Chem. 2003, 38, 173-182.
6. Tantillo, C.; Ding, J.; Jacobo-Molina, A.; Nanni, R. G.; Boyer, P. L.; Hughes, S. H.; Pauwels, R.; Andries, K.; Janssen, P. A.; Arnold, E. Locations of anti-AIDS drug binding sites and resistance mutations in the three-dimensional structure of HIV-1 reverse transcriptase. Implications for mechanisms of drug inhibition and resistance. J. Mol. Biol. 1994, 243, 369-387.
7. Spence, R. A.; Kati, W. M.; Anderson, K. S.; Johnson, K. A. Mechanism of inhibition of HIV-1 reverse transcriptase by nonnucleoside inhibitors. Science 1995, 267, 988-993.
8. Buckheit, R. W. Nonnucleoside reverse transcriptase inhibitors: Perspectives on novel therapeutic compounds and strategies for the treatment of HIV infection. Exp. Opin. Invest. Drugs 2001, 10, 1423-1442.
9. Artico, M. Nonnucleoside anti-HIV-1 reverse transcriptase inhibitors (NNRTIs): A chemical survey from lead compounds to selected drugs for clinical trials. Farmaco 1996, 51, 305-331.
10. Flynn, D. L. Abstracts 127-130 of 226th ACS National Meeting, New York, September 7-11, 2003.
11. De Clercq, E. New anti-HIV agents and targets. Med. Res. Rev. 2002, 22, 531-565.
12. De Clercq, E. Nonnucleoside reverse transcriptase inhibitors (NNRTIs): Past, present and future. Chem. Biodiversity 2004, 1, 44-64.
13. Williams, T. M.; Ciccarone, T. M.; MacTough, S. C.; Rooney, C. S.; Balani, S. K.; Condra, J. H.; Emini, E. A.; Goldman, M. E.; Greenlee, W. J.; Kauffman, L. R.; et al. 5-chloro-3-(phenylsulfonyl)indole-2-carboxamide: A novel, non-nucleoside inhibitor of HIV-1 reverse transcriptase. J. Med. Chem. 1993, 36, 1291-1294.
14. Young, S. D.; Amblard, M. C.; Brichter, S. F.; Grey, V. E.; Tran, L. O.; Lumma, W. C. J.; Huff, J. R.; Schleif, W. A.; Emini, E. E.; O'Brien, J. A.; Pettibone, D. J. 2-Heterocyclic indole-3-sulfones as inhibitors of HIV-1 reverse transcriptase. Bioorg. Med. Chem. Lett. 1995, 5, 491-496.
15. Artico, M.; Silvestri, R.; Stefancich, G.; Massa, S.; Pagnozzi, E.; Musu, D.; Scintu, F.; Pinna, E.; Tinti, E.; La Colla, P. Synthesis of pyrryl aryl sulfones targeted at the HIV-1 reverse transcriptase. Arch. Pharm. (Weinheim) 1995, 328, 223-229.
16. Artico, M.; Silvestri, R.; Massa, S.; Loi, A. G.; Corrias, S.; Piras, G.; La Colla, P. 2-Sulfonyl-4-chloroanilino moiety: A potent pharmacophore for the anti-human immunodeficiency virus type 1 activity of pyrrolyl aryl sulfones. J. Med. Chem. 1996, 39, 522-530.
17. Artico, M.; Silvestri, R.; Pagnozzi, E.; Bruno, B.; Novellino, E.; Greco, G.; Massa, S.; EtTorre, A.; Loi, A. G.; Scintu, F.; La Colla, P. Structure-based design, synthesis, and biological evaluation of novel pyrrolyl aryl sulfones: HIV-1 non-nucleoside reverse transcriptase inhibitors active at nanomolar concentrations. J. Med. Chem. 2000, 43, 1886-1891.
18. Silvestri, R.; De Martino, G.; La Regina, G.; Artico, M.; Massa, S.; Vargiu, L.; Mura, M.; Loi, A. G.; Marceddu, T.; La Colla, P. Novel indolyl aryl sulfones active against HIV-1 carrying NNRTI resistance mutations: Synthesis and SAR studies. J. Med. Chem. 2003, 46, 2482-2493.
19. Ren, J.; Diprose, J.; Warren, J.; Esnouf, R. M.; Bird, L. E.; Ikemizu, S.; Slater, M.; Milton, J.; Balzarini, J.; Stuart, D. I.; Stammers, D. K. Phenylethylthiazolylthiourea (PETT) non-nucleoside inhibitors of HIV-1 and HIV-2 reverse transcriptases. Structural and biochemical analyses. J. Biol. Chem. 2000, 275, 5633-5639.
20. Hogberg M.; Sahlberg C.; Engelhardt P.; Noreen R.; Kangasmetsa J.; Johansson NG.; Oberg B.; Vrang L.; Zhang H.; BL, S.; Unge T.; Lovgren S.; Fridborg K.; K, B. Urea-PETT compounds as a new class of HIV-1 reverse transcriptase inhibitors. 3. Synthesis and further structure-activity relationship studies of PETT analogues. J. Med. Chem. 1999, 42, 4150-4160.
21. Ren, J.; Milton, J.; Weaver, K. L.; Short, S. A.; Stuart, D. I.; Stammers, D. K. Structural basis for the resilience of efavirenz (DMP-266) to drug resistance mutations in HIV-1 reverse transcriptase. Struct. Fold Des. 2000, 8, 1089-1094.
22. Pauwels, R.; Andries, K.; Debyser, Z.; Van Daele, P.; Schols, D.; Stoffels, P.; De Vreese, K.; Woestenborghs, R.; Vandamme, A. M.; Janssen, C. G.; et al. Potent and highly selective human immunodeficiency virus type 1 (HIV-1) inhibition by a series of alpha-anilinophenylacetamide derivatives targeted at HIV-1 reverse transcriptase. Proc. Nat. Ac. Sci. U.S.A. 1993, 90, 1711-1715.
23. Ding, J.; Das, K.; Moereels, H.; Koymans, L.; Andries, K.; Janssen, P. A.; Hughes, S. H.; Arnold, E. Structure of HIV-1 RT/TIBO R 86183 complex reveals similarity in the binding of diverse nonnucleoside inhibitors. Nat. Struct. Biol. 1995, 2, 407-415.
24. Chan, J. H.; Hong, J. S.; Hunter, R. N. r.; Orr, G. F.; Cowan, J. R.; Sherman, D. B.; Sparks, S. M.; Reitter, B. E.; Andrews, C. W. r.; Hazen, R. J.; St Clair, M.; Boone, L. R.; Ferris, R. G.; Creech, K. L.; Roberts, G. B.; Short, S. A.; Weaver, K.; Ott, R. J.; Ren, J.; Hopkins, A.; Stuart, D. I.; Stammers, D. K. 2-Amino6-arylsulfonylbenzonitriles as non-nucleoside reverse transcriptase inhibitors of HIV-1. J. Med. Chem. 2001, 44, 1866-1882.
25. Hopkins, A. L.; Ren, J.; Esnouf, R. M.; Willcox, B. E.; Jones, E. Y.; Ross, C.; Miyasaka, T.; Walker, R. T.; Tanaka, H.; Stammers, D. K.; Stuart, D. I. Complexes of HIV-1 reverse transcriptase with inhibitors of the HEPT series reveal conformational changes relevant to the design of potent non-nucleoside inhibitors. J. Med. Chem. 1996, 39, 1589-1600.
26. Ren, J.; Esnouf, R. M.; Hopkins, A. L.; Jones, E. Y.; Kirby, I.; Keeling, J.; Ross, C. K.; Larder, B. A.; Stuart, D. I.; Stammers, D. K. 3′-Azido-3′-deoxythymidine drug resistance mutations in HIV-1 reverse transcriptase can induce long range conformational changes. Proc. Nat. Ac. Sci. U.S.A. 1998, 95, 9518-9523.
27. Barnard, J.; Borkow, G.; Parniak, M. A. The thiocarboxanilide nonnucleoside UC781 is a tight-binding inhibitor of HIV-1 reverse transcriptase. Biochemistry 1997, 36, 7786-7792.
28. Ren, J.; Esnouf, R. M.; Hopkins, A. L.; Warren, J.; Balzarini, J.; Stuart, D. I.; Stammers, D. K. Crystal structures of HIV-1 reverse transcriptase in complex with carboxanilide derivatives. Biochemistry 1998, 37, 14394-14403.
29. Kohlstaedt, L. A.; Wang, J.; Friedman, J. M.; Rice, P. A.; Steitz, T. A. Crystal structure at 3.5 Å resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science 1992, 256, 1783-1790.
30. Goodsell, D. S.; Morris, G. M.; Olson, A. J. Automated docking of flexible ligands: Applications of AutoDock. J. Mol. Recog. 1996, 9, 1-5.
31. Ragno, R. Cross-Docking: Applcation to HIV-NNRTI inhibitors. Manuscript in Preparation.
32. Sippl, W.; Contreras, J. M.; Parrot, I.; Rival, Y. M.; Wermuth, C. G. Structure-based 3D QSAR and design of novel acetylcholinesterase inhibitors. J. Comput. Aided Mol. Des. 2001, 15, 395-410.
33. Sippl, W. Receptor-based 3D QSAR analysis of estrogen receptor ligands - Merging the accuracy of receptor-based alignments with the computational efficiency of ligand-based methods. J. Comput. Aided Mol. Des. 2000, 14, 559-572.
34. Lewis, P. J.; de Jonge, M.; Daeyaert, F.; Koymans, L.; Vinkers, M.; Heeres, J.; Janssen, P. A.; Arnold, E.; Das, K.; Clark, A. D., Jr.; Hughes, S. H.; Boyer, P. L.; de Bethune, M. P.; Pauwels, R.; Andries, K.; Kukla, M.; Ludovici, D.; De Corte, B.; Kavash, R.; Ho, C. On the detection of multiple-binding modes of ligands to proteins, from biological, structural, and modeling data. J. Comput. Aided Mol. Des. 2003, 17, 129-134.
35. Goodford, P. J. A computational procedure for determining energetically favorable binding sites on biologically important macromolecules. J. Med. Chem. 1985, 28, 849-857.
36. Pastor, M.; Cruciani, G.; Watson, K. A. A strategy for the incorporation of water molecules present in a ligand binding site into a three-dimensional quantitative structure-activity relationship analysis. J. Med. Chem. 1997, 40, 4089-4102.
37. Baroni, M.; Costantino, G.; Cruciani, G.; Riganelli, D.; Valigi, R.; Clementi, S. Generating optimal linear PLS estimations (GOLPE): An advanced chemometric tool for handling 3D-QSAR problems. Quant. Struct.-Act. Relat. 1993, 12, 9-20.
38. Cytotoxicities determinations and antiviral tests have been performed at Dipartimento di Scienze e Tecnologie Biomediche, Sezione di Microbiologia e Virologia Generale e Biotecnologie Microbiche, University of Cagliari (Italy).
39. Pauwels, R.; Andries, K.; Debyser, Z.; Kukla, M. J.; Schols, D.; Breslin, H. J.; Woestenborghs, R.; Desmyter, J.; Janssen, M. A.; De Clercq, E.; et al. New tetrahydroimidazo[4,5,1-jk][1,4]-benzodiazepin-2(1H)-one and -thione derivatives are potent inhibitors of human immunodeficiency virus type 1 replication and are synergistic with 2′,3′-dideoxynucleoside analogues. Antimicrob. Agents Chemother. 1994, 38, 2863-2870.
40. Tafi, A.; Anastassopoulou, J.; Theophanides, T.; Botta, M.; Corelli, F.; Massa, S.; Artico, M.; Costi, R.; Di Santo, R.; Ragno, R. Molecular modeling of azole antifungal agents active against Candida albicans. 1. A comparative molecular field analysis study. J. Med. Chem. 1996, 39, 1227-1235.
41. Ragno, R.; Marshall, G. R.; Di Santo, R.; Costi, R.; Massa, S.; Rompei, R.; Artico, M. Antimycobacterial pyrroles: Synthesis, anti-Mycobacterium tuberculosis activity and QSAR studies. Bioorg. Med. Chem. 2000, 8, 1423-1432.
42. Mohamadi, F.; Richards, N. G. J.; Guida, W. C.; Liskamp, R.; Lipton, M.; Caufield, C.; Chang, G.; Hendrickson, T.; Still, W. C. MacroModel-An Integrated Software System for Modeling Organic and Bioorganic Molecules Using Molecular Mechanics. J. Comput. Chem. 1990, 11, 440-467.
43. Pearlman, D. A.; Case, D. A.; Caldwell, J. W.; Ross, W. S.; Cheatham, I.; Thomas E.; DeBolt, S.; Ferguson, D.; Seibel, G.; Kollman, P. AMBER, a package of computer programs for applying molecular mechanics, normal-mode analysis, molecular dynamics and free energy calculations to simulate the structural and energetic properties of molecules. Comput. Phys. Commun. 1995, 91, 1-41.
44. Berman, H.; Henrick, K.; Nakamura, H. Announcing the worldwide Protein Data Bank. Nat. Struct. Biol. 2003, 10, 980.
45. Pastor, M.; Cruciani, G.; Clementi, S. Smart region definition: A new way to improve the predictive ability and interpretability of three-dimensional quantitative structure-activity relationships. J. Med. Chem. 1997, 40, 1455-1464.