Development of a novel virtual screening cascade protocol to identify potential trypanothione reductase inhibitors

Journal of Medicinal Chemistry

Volumn 52, Issue 6, 2009, Pages 1670-1680

  Perez Pineiro, Rolando ^a   Burgos, Asdrubal ^a   Jones, Deuan C ^b   Andrew, Lena C ^a   Rodriguez, Hortensia ^c   Suarez, Margarita ^c   Fairlamb, Alan H ^b   Wishart, David S ^a  

^a UNIVERSITY OF ALBERTA   (Canada)

^b UNIVERSITY OF DUNDEE   (United Kingdom)

^c UNIVERSITY OF HAVANA   (Cuba)

Author keywords

[No Author keywords available]

Indexed keywords

1 (10,11 DIHYDRODIBENZO[B,F]THIEPIN 10 YL) 4 ETHYLPIPERAZIN 1,4 DIIUM; 2 (3 (2 CHLORO 10H PHENOTHIAZIN 0 YL) 3 OXOPROPYL)DECAHYDROPYRIDO[1,2 A]PYRAZINE 2,5 DIIUM; 2,4,6 TRIOXOHEXAHYDROPYRIMIDINE; 3 ((10H PHENOTHIPHENOTHIAZIN 10- L)METHYL) 1 AZONIABICYCLO[2.2.2]OCTANE; 3 ((11H DIBENZO[B,E][1,4]OXATHIEPIN 11 YL)METHYL) 1 METHYLPIPERIDINIUM; 3 (11H DIBENZO[B,E][1,4]DITHIEPIN 11 YL) N,N DIMETHYLPROPAN 1 AMINIUM; ANTIPROTOZOAL AGENT; N METHYL N (2 OXO 2 (2 (PHENYLTHIO)PHENYLAMINO)ETHYL)CYCLOHEXANAMINIUM; OXIDOREDUCTASE INHIBITOR; TRYPANOTHIONE REDUCTASE INHIBITOR DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DRUG EFFECT; DRUG INHIBITION; DRUG SCREENING; DRUG STRUCTURE; NONHUMAN; TRYPANOSOMA BRUCEI; TRYPANOSOMA CRUZI;

CLUSTER ANALYSIS; ENZYME INHIBITORS; MODELS, MOLECULAR; NADH, NADPH OXIDOREDUCTASES;

EID: 64549124228     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm801306g     Document Type: Article

References (53)

1. Sachs, J. D.; Hotez, P. J. Fighting tropical diseases. Science 2006, 311, 1521.
2. Renslo, A. R.; McKerrow, J. H. Drug discovery and development for neglected parasitic diseases. Nat. Chem. Biol. 2006, 2, 701-710.
3. Nwaka, S.; Hudson, A. Innovative lead discovery strategies for tropical diseases. Nat. Rev. Drue Discovery 2006, 5, 941-955.
4. Fairlamb, A. H.; Blackburn, P.; Ulrich, P.; Chait, B. T.; Cerami, A. Trypanothione: a novel bis(glutathionyl)spermidine cofactor for glutathione reductase in trypanosomatids. Science 1985, 227, 1485-1487.
5. Krauth-Siegel, R. L.; Bauer, H.; Schirmer, H. Dithiol proteins as guardians of the intracellular redox milieu in parasites: old and new drugs targets in trypanosomes and malaria-causing plasmodia. Aneew. Chem., Int. Ed. 2005, 44, 690-715.
6. O'Sullivan, M. C. The battle against trypanosomiasis and leishmaniasis: metal-based and natural product inhibitors of trypanothione reductase. Curr. Med. Chem. 2005, 4, 355-378.
7. Lange, G. Structure-based drug design-the use of protein structure in drug discovery. In Comprehensive Medicinal Chemistry II, 1st ed.; Triggle, D. J., Taylor, J. B., Eds.; Elsevier, Oxford, 2006; Vol. 4; pp 597-650.
8. Wolf, K.; Dormeyer, M. Information-based methods in the development of antiparasitic drugs. ParasitolRes. 2003, 90, S91-S96.
9. Kuriyan, J.; Kong, X. P.; Krishna, T. S.; Sweet, R. M.; Murgolo, N. J.; Field, H.; Cerami, A.; Henderson, G. B. X-Ray Structure of Trypanothione Reductase from Crithidiafasciculata at 2.4 A Resolution. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 8764-8768.
10. Hunter, W. N.; Bailey, S.; Habash, J.; Harrop, S. J.; Helliwel, J. R.; Aboagye-Kwarteng, T.; Smith, K.; Fairlamb, A. H. Active site of trypanothione reductase: A target for rational drug design. J. Mol. Biol. 1992, 227, 322-333.
11. Lantwin, C. B.; Schlichting, I.; Kabsch, W.; Pai, E. F.; Krauth-Siegel, R. L. The structure of Trypanosoma cruzi trypanothione reductase in the oxidized and NADPH reduced state. Proteins 1994, 18, 161-173.
12. Bailey, S.; Smith, K.; Fairlamb, A. H.; Hunter, W. N. Substrate interactions between trypanothione reductase and W-glutathionylsper-midine disulphide at 0.28 nm resolution. Eur. J. Biochem. 1993, 213, 67-75.
13. Bond, C. S.; Zhang, Y.; Berriman, M.; Cunningham, M. L.; Fairlamb, A. H.; William, N. H. Crystal structure of Trypanosoma cruzi trypanothione reductase in complex with trypanothione, and the structure-based discovery of new natural product inhibitors. Structure 1999, 7, 81-89.
14. Jacoby, E. M.; Schlichting, I.; Lantwin, C. B.; Kabsch, W.; Krauth-Siegel, R. L. Crystal structure of the Trypanosoma cruzi trypanothione reductase · mepacrine complex. Proteins 1996, 24, 73-80.
15. Saravanamuthu, A.; Vickers, T. J.; Bond, C. S.; Peterson, M. R.; Hunter, W. N.; Fairlamb, A. H. Two interacting binding sites for quinacrine derivatives in the active site of trypanothione reductase: A template for drug design. J. Biol. Chem. 2004, 279, 29493-29500.
16. Horvath, D. A virtual screening approach applied to the search for trypanothione reductase inhibitors. J. Med. Chem. 1997, 40, 2412-2423.
17. Meiering, S.; Inhoff, O.; Mies, J.; Vincek, A.; Garcia, G.; Kramer, B.; Dormeyer, M.; Krauth-Siegel, R. L. Inhibitors of Trypanosoma cruzi trypanothione reductase revealed by virtual screening and parallel synthesis. J. Med. Chem. 2005, 48, 4793-802.
18. Garforth, J.; Yin, H.; McKie, J. H.; Douglas, K. T.; Fairlamb, A. H. Rational design of selective ligands for trypanothione reductase from Trypanosoma cruzi. Structural effects on the inhibition by dibenza-zepines based on imipramine. J. Enzyme Inhib. 1997, 12, 161-173.
19. Khan, M. O.; Austin, S. E.; Chan, C.; Yin, H.; Marks, D.; Vaghjiani, S. N.; Kendrick, H.; Yardley, V.; Croft, S. L.; Douglas, K. T. Use of an additional hydrophobic binding site, the Z site, in the rational drug design of a new class of stronger trypanothione reductase inhibitor, quaternary alkylammonium phenothiazines. J. Med. Chem. 2000, 43, 3148-3156.
20. Bonse, S.; Santelli-Rouvier, C.; Barbe, J.; Krauth-Siegel, R. L. Inhibition of Trypanosoma cruzi trypanothione reductase by acridines: Kinetic studies and structure- activity relationships. J. Med. Chem. 1999, 42, 5448-5454.
21. Ponasik, J. A.; Strickland, C.; Faerman, C.; Savvides, S.; Karplus, P. A.; Ganem, B. Kukoamine A and other hydrophobic acylpolyamines: potent and selective inhibitors of Crithidia fasciculata trypanothione reductase. Biochem. J. 1995, 311, 371-375.
22. Fradera, X.; Knegtel, M. A.; Mestres, J. Similarity-driven flexible ligand docking. Proteins 2000, 40, 623-626.
23. Wu, G.; Vieth, M. SDOCKER: A method utilizing existing X-ray structures to improve docking accuracy. J. Med. Chem. 2004, 47, 3142-3148.
24. Kortagere, S.; Welsh, W. J. Development and application of hybrid structure based method for efficient screening of ligands binding to G-protein coupled receptors. J. Comput.-Aided Mol. Des. 2006, 20, 789-802.
25. Marialke, J.; Tietze, S.; Apostolakis, J. Similarity Based Docking. J. Chem., Inf. Model. 2008, 48, 186-196.
26. Bajorath, J. Selected concepts and investigations in compound classification, molecular descriptors analysis, and virtual screening. J. Chem. Inf. Comput. Sci. 2001, 41, 233-245.
27. Batista, J.; Bajorath, J. Chemical database mining through entropy-based molecular similarity assessment of randomly generated structural fragment populations. J Chem. Inf Com Comput Sci. 2007, 47, 59-68.
28. Bajorath, J. Integration of virtual and high-throughput screening. Nat. Rev. Drug Discovery 2002, 1, 882-894.
29. (a) Monzote, L.; Montalvo, A. M.; Fonseca, L.; Perez, R.; Suarez, M.; Rodriguez, H. In vitro activities of thiadiazine derivatives against Leishmania amazonensis. Arzneim. Forschung./Drug Res. 2005, 55, 232-238.
30. (b) Coro, J.; Atherton, R.; Little, S.; Wharton, H.; Yardley, V.; Alvarez, A, Jr.; Suarez, M; Perez, R.; Rodriguez, H. Alkyl-linked bis-THTT derivatives as potent in vitro trypanocidal agents. Bioorg. Med. Chem. Lett. 2006, 16, 1312-1315.
31. Miscreen-Molinspiration Fragment-based Virtual Screening Engine written in Java; http://www.molinspiration.com/docu/miscreen/index.html. Accessed February 15, 2007.
32. Miteva, M. A.; Violas, S.; Montes, M.; Gomez, D.; Tuffery, P.; Villoutreix, B. O. FAF-Drugs: free ADME/tox filtering of compound collections. Nucleic Acids Res. 2006, 34, W738-W744.
33. Faerman, C. H.; Sawides, S. N.; Strickland, C.; Breidenbach, M. A.; Ponasik, J. A.; Ganem, B.; Ripoll, D.; Krauth-Siegel, R. L.; Karplus, P. A. Charge is the major discriminating factor for glutathione reductase versus trypanothione reductase inhibitors. Bioorg. Med. Chem. 1996, 4, 1247-1253.
34. Chemaxon; http://www.chemaxon.com. Accessed December 14, 2007.
35. Huey, R.; Morris, G. M.; Olson, A. J.; Goodsell, D. S. A Semiempirical Free Energy Force Field with Charge-Based Desolvation. J. Comput. Chem. 2007, 28, 1145-1152.
36. Morris, G. M.; Goodsell, D. S.; Halliday, R. S.; Huey, R.; Hart, W. E.; Belew, R. K.; Olson, A. J. Automated Docking Using a Lamarckian Genetic Algorithm and an Empirical Binding Free Energy Function. J. Comput. Chem. 1998, 19, 1639-1662.
37. Zhang, Y.; Bond, C. S.; Bailey, S.; Cunningham, M. L.; Fairlamb, A. H.; Hunter, W. N. The crystal structure of trypanothione reductase from the human pathogen Trypanosoma cruzi at 2.3 A resolution. Protein Sci. 1996, 5, 52-61.
38. Irwin, J. J.; Shoichet, B. K. ZINC-A Free Database of Commercially Available Compounds for Virtual Screening. J. Chem. Inf. Model. 2005, 45, 177-182.
39. Wang, R.; Lai, L.; Wang, S. Further development and validation of empirical scoring functions for structure-based binding affinity prediction. J. Comput.-Aided Mol. Des. 2002, 16, 11-26.
40. DeLano, W. L. The PyMOL Molecular Graphics System, DeLano Scientific: Palo Alto, CA, 2002; http://www.pymol.org.
41. Wallace, A. C.; Laskowski, R. A.; Thornton, J. M. LIGPLOT: a program to generate schematic diagrams of protein- ligand interactions. Protein Eng. 1995, 8, 127-134.
42. Yang, J. M.; Chen, Y. F.; Shen, T. W.; Kristal, B. S.; Hsu, D. F. Consensus scoring criteria for improving enrichment in virtual screening. J. Chem. Inf. Model. 2005, 45, 1134-1146.
43. Cummings, M. D.; Desjarlais, R. L.; Gibbs, A. C.; Mohan, V.; Jaeger, E. P. Comparison of automated docking programs as virtual screening tools. J. Med. Chem. 2005, 48, 962-976.
44. Lindstrom, W.; Morris, G. M.; Weber, C.; Huey, R. Using AutoDock for virtual screening; The Scripps Research Institute Molecular Graphics Laboratory: La Jolla, CA, 2006; pp 1 - 36.
45. Wang, R.; Lu, Y.; Wang, S. Comparative Evaluation of 11 Scoring Functions for Molecular Docking. J. Med. Chem. 2003, 46, 2287-2303.
46. Wang, R.; Wang, S. How does consensus scoring work for virtual library screening? An idealized computer experiment. J. Chem. Inf. Comput. Sci. 2001, 41, 1422-1426.
47. Parveen, S.; Khan, M. O. F.; Austin, S. E.; Croft, S. L.; Yardley, V.; Rock, P.; Douglas, K. T. Antitrypanosomal, antileishmanial, and antimalarial activities of quaternary arylalkylammonium 2-amino-4-chlorophenyl sulfides, a new class of trypanothione reductase inhibitor, and of N-acylderivatives of 2-amino-4-chlorophenyl phenyl sulfide. J. Med. Chem. 2005, 48, 8087-8097.
48. Hamilton, C. J.; Saravanamuthu, A.; Egglestone, I. M.; Fairlamb, A. H. Ellman's-reagent-mediated regeneration of trypanothione in situ: substrate-economical microplate and time-dependent inhibition assays for trypanothione reductase. Biochem. J. 2003, 369, 529-537.
49. Zhang, J.-H.; Chung, T. D. Y.; Oldenburg, K. R. A simple statistical parameter for use in evaluation and validation of high throughput screening assays. J. Biomol. Screen 1999, 4, 67-73.
50. Lal, B.; Sharma, S.; Ghosh, U.; Bal-Tembe, S.; More, T.; Gagare, P.; Jadhav, S.; Patil, S.; Kulkarni-Almeida, A.; Parikh, S.; Panicker, R.; Damre, A.; Gupte, R. Fused tricyclic compounds as inhibitors of tumor necrosis factor-a, their preparation, pharmaceutical compositions, and use in therapy. PCT Int. Appl. WO 2006051477, 2006; p 115.
51. Dubaele, S.; Jahnke, W.; Schoepfer, J.; Fuchs, J.; Chene, P. Inhibition of DNA helicases with DNA-competitive inhibitors. Bioorg. Med. Chem. Lett. 2006, 16, 923-927.
52. Sindelar, K.; Holubek, J.; Ryska, M.; Svatek, E.; Dlabac, A.; Hrubantova, M.; Protiva, M. Neurotropic and psychotropic agents. CLXI. Tricyclic psychotropic agents containing two chalcogen atoms in the central ring: synthesis of 11-(dimethylaminoalkyl) derivatives of 11H-dibenzo[b,e]-1,4- dioxepin and 11H-dibenzo[b,e]-1,4-dithiepin. Collect. Czech. Chem. Commun. 1982, 47, 72-87.
53. Bi, X.; Lopez, C.; Bacchi, C. J.; Rattendi, D.; Woster, P. M. Novel alkylpolyaminoguanidines and alkylpolyaminobiguanides with potent antitrypanosomal activity. Bioorg. Med. Chem. Lett. 2006, 16, 3229-3232.