Rational design of 5′-thiourea-substituted α-thymidine analogues as thymidine monophosphate kinase inhibitors capable of inhibiting mycobacterial growth

Journal of Medicinal Chemistry

Volumn 50, Issue 22, 2007, Pages 5281-5292

  Van Daele, Ineke ^a   Munier Lehmann, Hélène ^b   Froeyen, Matheus ^c   Balzarini, Jan ^c   Van Calenbergh, Serge ^a  

^a GHENT UNIVERSITY   (Belgium)

^b INSTITUT PASTEUR   (France)

^c REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

(3 TRIFLUOROMETHYL 4 CHLOROPHENYL)THIOUREA DERIVATIVE; 5' THIOUREA DERIVATIVE; ALPHA THYMIDINE DERIVATIVE; BACTERIAL ENZYME; ENZYME INHIBITOR; GROWTH INHIBITOR; NUCLEOSIDE; THIOUREA; THYMIDINE MONOPHOSPHATE KINASE INHIBITOR; THYMIDYLATE KINASE; THYMINE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANTIBACTERIAL ACTIVITY; ARTICLE; BACTERIAL GROWTH; BACTERIAL STRAIN; CONCENTRATION RESPONSE; CYTOTOXICITY; DRUG BINDING; DRUG DESIGN; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; MINIMUM INHIBITORY CONCENTRATION; MYCOBACTERIUM BOVIS; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; SUBSTITUTION REACTION; X RAY STRUCTURE;

ANIMALS; ANTI-BACTERIAL AGENTS; CERCOPITHECUS AETHIOPS; CRYSTALLOGRAPHY, X-RAY; DIMERIZATION; HUMANS; MODELS, MOLECULAR; MYCOBACTERIUM; MYCOBACTERIUM BOVIS; MYCOBACTERIUM TUBERCULOSIS; NUCLEOSIDE-PHOSPHATE KINASE; NUCLEOSIDES; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; THIOUREA; THYMIDINE; VERO CELLS;

EID: 35848946837     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0706158     Document Type: Article

References (49)

1. World Health Organization (http://www.who.org), 2006.
2. Blumberg, H. M.; et al. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: Treatment of tuberculosis. Am. J. Respir. Crit. Care Med. 2003, 167, 603-662.
3. Bucher, H. C.; Griffith, L. E.; Guyatt, G. H.; Sudre, P.; Naef, M.; Sendi, P.; Battegay, M. Isoniazid prophylaxis for tuberculosis in HIV infection: a meta-analysis of randomized controlled trials. AIDS 1999, 13, 501-507.
4. Daley, C. L.; Small, P. M.; Schecter, G. F.; Schoolnik, G. K.; McAdam, R. A.; Jacobs, W. R.; Hopewell, P. C. An outbreak of tuberculosis with accelerated progression among persons infected with the human immunodeficiency virus: an analysis using restriction-fragment-length polymorphisms. N. Engl. J. Med. 1992, 326, 231-235.
5. Gao, L. Y.; Laval, F.; Lawson, E. H.; Groger, R. K.; Woodruff, A.; Morisaki, J. H.; Cox, J. S.; Daffe, M.; Brown, E. J. Requirement for kasB in Mycobacterium mycolic acid biosynthesis, cell wall impermeability and intracellular survival: implications for therapy. Mol. Microbiol. 2003, 49, 1547-1563.
6. Zhang, Y.; Post-Martens, K.; Denkin, S. New drug candidates and therapeutic targets for tuberculosis therapy. Drug Discovery Today 2006, 11, 21-27.
7. Andries, K.; Verhasselt, P.; Guillemont, J.; Gohlmann, H. W.; Neefs, J. M.; Winkler, H.; Van Gestel, J.; Timmerman, P.; Zhu, M.; Lee, E.; Williams, P.; de Chaffoy, D.; Huitric, E.; Hoffner, S.; Cambau, E.; Truffot-Pernot, C.; Lounis, N.; Jarlier, V. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science 2005, 307, 223-227.
8. Munier-Lehmann, H.; Chafotte, A.; Pochet, S.; Labesse, G. Thymidylate kinase of Mycobacterium tuberculosis: a chimera sharing properties common to eukaryotic and bacterial enzymes. Protein Sci. 2001, 10, 1195-1205.
9. Ostermann, N.; Schlichting, I.; Brundiers, R.; Konrad, M.; Reinstein, J.; Veit, T.; Goody, R. S.; Lavie, A. Insights into the phosphoryltransfer mechanism of human thymidylate kinase gained from crystal structures of enzyme complexes along the reaction coordinate. Structure 2000, 8, 629-642.
10. Lavie, A.; Schlichting, I.; Vetter, I. R.; Konrad, M.; Reinstein, J.; Goodey, R. S. The bottleneck in AZT activation. Nat. Med. 1997, 3, 922-924.
11. Li de la Sierra, I.; Munier-Lehmann, H.; Gilles, A. M.; Bârzu, O.; Delarue, M. X-ray structure of TMP kinase from Mycobacterium tuberculosis complexed with TMP at 1.95 Å resolution. J. Mol. Biol. 2001, 311, 87-100.
12. Vanheusden, V.; Munier-Lehmann, H.; Froeyen, M.; Busson, R.; Rozenski, J.; Herdewijn, P.; Van Calenbergh, S. Discovery of bicyclic thymidine analogues as selective and high affinity inhibitors of Mycobacterium tuberculosis thymidine monophosphate kinase. J. Med. Chem. 2004, 47, 6187-6194.
13. Vanheusden, V.; Munier-Lehmann, H.; Pochet, S.; Herdewijn, P.; Van Calenbergh, S. Synthesis and biological evaluation of thymidine-5′-O- monophosphate analogues as inhibitors of M. tuberculosis thymidylate kinase. Bioorg. Med. Chem. Lett. 2002, 12, 2695-2698.
14. Vanheusden, V.; Van Rompaey, P.; Munier-Lehmann, H.; Pochet, S.; Herdewijn, P.; Van Calenbergh, S. Thymidine and thymidine-5′-O- monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase. Bioorg. Med. Chem. Lett. 2003, 13, 3045-3048.
15. Haouz, A.; Vanheusden, V.; Munier-Lehmann, H.; Froeyen, M.; Herdewijn, P.; Van Calenbergh, S.; Delarue, M. Enzymatic and structural analysis of inhibitors designed against M. tuberculosis thymidylate kinase: new insights into the phosphoryl transfer mechanism. J. Biol. Chem. 2003, 278, 4963-4971.
16. Pochet, S.; Dugue, L.; Labesse, G.; Delepierre, M.; Munier-Lehmann, H. Comparative study of purine and pyrimidine nucleoside analogues acting on the thymidylate kinases of Mycobacterium tuberculosis and of humans. ChemBioChem 2003, 4, 742-747.
17. Van Daele, I.; Munier-Lehmann, H.; Hendrickx, P. M. S.; Marchal, G.; Chavarot, P.; Froeyen, M.; Qing, L.; Martins, J. C.; Van Calenbergh, S. Synthesis and biological evaluation of bicyclic nucleosides as inhibitors of M. tuberculosis thymidylate kinase. ChemMedChem 2006, 1, 1081-1090.
18. Phetsuksiri, B.; Jackson, M.; Scherman, H.; McNeil, M.; Besra, G. S.; Baulard, A. R.; Slayden, R. A.; DeBarber, A. E.; Barry, C. E., III; Baird, M. S.; Crick, D. C.; Brennan, P. J. Unique mechanism of action of the thiourea drug isoxyl on Mycobacterium tuberculosis. J. Biol. Chem. 2003, 278, 53123-53130.
19. Urbancik, B. A clinical trial of thiocarlide (isoxyl). Tubercle 1966, 47, 283-288.
20. Urbancik, B. Clinical experiences with thiocarlide (isoxyl). Antibiot. Chemother. 1970, 16, 117-123.
21. Topliss, J. G. Utilization of operational schemes for analog synthesis in drug design. J. Med. Chem. 1972, 15, 1006.
22. Ferreras, J.; Ryu, J.-S.; Di Lello, F.; Tan, D. S.; Quadri, L. E. N. Small-molecule inhibition of siderophore biosynthesis in Mycobacterium tuberculosis and Yersinia pestis. Nat. Chem. Biol. 2005, 1, 29-32.
23. Somu, R. V.; Boshoff, H.; Qiao, C.; Bennet, E. M.; Barry, C. E., III; Aldrich, C. C. Rationally designed nucleoside antibiotics that inhibit siderophore biosynthesis of Mycobacterium tuberculosis. J. Med. Chem. 2006, 49, 31-34.
24. Faul, M. M.; Huff, B. E.; Dunlap, S. E.; Frank, S. A.; Fritz, J. E.; Kaldor, S. W.; LeTourneau, M. E.; Staszak, M. A.; Ward, J. A.; Werner, J. A.; Winneroski, L. L. Synthesis of 2′,3′-dideoxy-3′- hydroxymethylcytidine; a unique antiviral nucleoside. Tetrahedron 1997, 24, 8085-8104.
25. Peoc'h, D.; Swayze, E. E.; Bhat, B.; Sanghvi, Y. S. Synthesis of 2′-substituted MMI linked nucleosidic dimers: an optimization study in search of high affinity oligonucleotides for use in antisense constructs. Nucleosides Nucleotides 2004, 23, 411-438.
26. Chu, C. K.; Doboszewski, B.; Schmidt, W.; Ullas, G. V.; Van Roey, P. Synthesis of pyrimidine 3′-allyl-2′,3′-dideoxyribonucleosides by free-radical coupling. J. Org. Chem. 1989, 54, 2767-2769.
27. Ward, D. I.; Jeffs, S. M.; Coe, P. L.; Walker, R. T. A mild procedure for the anomerization of 2′-deoxynucleosides. Tetrahedron Lett. 1993, 34, 6779-6782.
28. Danel, K.; Larsen, E.; Pedersen, E. B. Easy synthesis of 5,6-disubstituted acyclouridine derivatives. Synthesis 1995, 8, 934-936.
29. Ciuffreda, P.; Loseto, A.; Santaniello, E. Deamination of 5′-substituted-2′,3′-isopropylidene adenosine derivatives catalyzed by adenosine deaminase and complementary enzymatic biotransformations catalyzed by adenylate deaminase: a viable route for the preparation of 5′-substituted inosine derivatives. Tetrahedron 2002, 58, 5767-5771.
30. Hansch, C.; Fujita, T. ρ-σ-π analysis. A method for the correlation of biological activity and chemical structure. J. Am. Chem. Soc. 1964, 86, 1616.
31. Wang, J.; Choudhury, D.; Chattopadhyaya, J.; Eriksson, S. Stereomeric selectivity of human deoxyribonucleoside kinase. Biochemistry 1999, 38, 16993-16999.
32. Wallace, A. C.; Laskowski, R. A.; Thornton, J. M. LIGPLOT - a program to generate schematic diagrams of protein-ligand interac-tions. Protein Eng., Des. Sel. 1995, 8, 127-134.
33. McDonald, I. K.; Thornton, J. M. Satisfying hydrogen bonding potential in proteins. J. Mol. Biol. 1994, 238, 777-793.
34. Krause, S.; Willighagen, E.; Steinbeck, C. JChemPaint - Using the collaborative forces of the internet to develop a free editor for 2D chemical structures. Molecules 2000, 5, 93-98.
35. Kraulis, P. J. MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures. J. Appl. Crystallogr. 1991, 24, 946-950.
36. Esnouf, R. M. Further additions to Molscript 1.4, including reading and contouring of electron-density maps. Acta Crystallogr., Sect. D 1999, 55, 938-940.
37. Merritt, E. A.; Bacon, D. J. Raster3D: photorealistic molecular graphics. Methods Enzymol. 1997, 277, 505-524.
38. Underwater, R. C. A.; Commandeur, J. N. M.; Vermeulen, N. P. E. Comparative cytotoxicity of N-substituted N′-(4-imidazole-ethyl) thiourea in precision-cut rat liver slices. Toxicology 2004, 197, 80-90.
39. Blondin, C.; Serina, L.; Wiesmuller, L.; Gilles, A. M.; Bârzu, O. Improved spectrophotometric assay of nucleoside monophosphate kinase activity using pyruvate kinase/lactate dehydrogenase coupling system. Anal. Biochem. 1994, 220, 219-222.
40. Palomino, J. C.; Martin, A.; Camacho, M.; Guerrra, H.; Swings, J. F. Portaels resazurin microtiter assay plate: simple and inexpensive method for detection of drug resistance in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 2002, 46, 2720-2722.
41. Collins, L.; Franzblau, S. G. Microplate alamar blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium. Antimicrob. Agents Chemother. 1997, 41, 1004-1009.
42. Krause, S.; Willighagen, E.; Steinbeck, C. JChemPaint - Using the collaborative forces of the internet to develop a free editor for 2D chemical structures. Molecules 2000, 5, 93-98.
43. Smith, D. H.; Gray, N. A. B.; Norse, J. G.; Crandell, C. W. The Dendral Project: recent advances in computer-assisted structure elucidation. Anal. Chim. Acta 1981, 133, 471-497.
44. Schmidt, M.; Baldridge, K.; Boatz, J.; Elbert, S.; Gordon, M.; Jensen, J.; Koseki, S.; Matsunaga, N.; Nguyen, K.; Su, S.; Windus, T.; Dupuis, M.; Montgomery, J. General atomic and molecular electronic structure system. J. Comput. Chem. 1993, 14, 1347-1363.
45. Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The Protein Data Bank. Nucleic Acids Res. 2000, 28, 235-242.
46. Allen, F. H. The CSD (Cambridge Structural Database) system: the Cambridge Structural Database: a quarter of a million crystal structures and rising. Acta Crystallogr. 2002, B58, 380-388.
47. Araki, K.; Wei, Q. Y.; O'Toole, J.; Toscano, P. J.; Welch, J. T. The synthesis of 2,3-dideoxy-2-fluoro-3-C-methylpentose-containing nucleosides via [3,3]-sigmatropic rearrangements. Carbohydr. Res. 1993, 249, 139-161.
48. Rogers, J. P.; Beuscher, A. E.; Flajolet, M.; Mcavoy, T.; Nairn, A. C.; Olson, A. J.; Greengard, P. Discovery of protein phosphatase 2C Inhibitors by virtual screening. J. Med. Chem. 2006, 19, 1658-1667.
49. 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 and empirical binding free energy function. J. Comput. Chem. 1998, 19, 1639-1662.