Rational design and 3D-pharmacophore mapping of 5′-thiourea- substituted α-thymidine analogues as mycobacterial TMPK inhibitors

Journal of Chemical Information and Modeling

Volumn 49, Issue 4, 2009, Pages 1070-1078

  Andrade, Carolina H ^a,b,c   Pasqualoto, Kerly F M ^a   Ferreira, Elizabeth I ^a   Hopfmger, Anton J ^b  

^a UNIVERSITY OF SÃO PAULO   (Brazil)

^b UNIVERSITY OF NEW MEXICO   (United States)

^c Faculty of Pharmaceutical Sciences   (Brazil)

Author keywords

[No Author keywords available]

Indexed keywords

BINDING SITES; COMPUTATIONAL CHEMISTRY; MOLECULAR GRAPHICS; MOLECULAR MODELING; PHARMACODYNAMICS; THIOUREAS;

ADMET PROPERTIES; ANTITUBERCULOSIS; CRYSTALLOGRAPHIC STRUCTURE; MYCOBACTERIUM TUBERCULOSIS; PHARMACOPHORE MAPPING; POTENT INHIBITOR; RATIONAL DESIGN; SOLID CONSISTENCY;

STRUCTURAL DESIGN;

DRUG DERIVATIVE; ENZYME INHIBITOR; LIGAND; NUCLEOSIDE MONOPHOSPHATE KINASE; THIOUREA; THYMIDINE; THYMIDYLATE KINASE; TUBERCULOSTATIC AGENT;

ALGORITHM; ARTICLE; CHEMICAL STRUCTURE; CHEMISTRY; CONFORMATION; DRUG ANTAGONISM; DRUG DESIGN; DRUG EFFECT; ENZYMOLOGY; MYCOBACTERIUM TUBERCULOSIS; QUANTITATIVE STRUCTURE ACTIVITY RELATION; REPRODUCIBILITY; SYNTHESIS;

ALGORITHMS; ANTITUBERCULAR AGENTS; DRUG DESIGN; ENZYME INHIBITORS; LIGANDS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; MYCOBACTERIUM TUBERCULOSIS; NUCLEOSIDE-PHOSPHATE KINASE; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; REPRODUCIBILITY OF RESULTS; THIOUREA; THYMIDINE;

EID: 66149117337     PISSN: 15499596     EISSN: 1549960X     Source Type: Journal    
DOI: 10.1021/ci8004622     Document Type: Article

References (30)

1. Dye, C.; Floyd, K.; Uplekar, M. Global tuberculosis control: surveillance, planning, financing. WHO Report 2008; World Health Organization Document, 2008. WHO/HTM/TB/2008.393.
2. Vilchèze, C.; Weissbrod, T. R.; Chen, B.; Kremer, L.; Hazbón, M. H.; Wang, F.; Alland, D.; Sacchettini, J. C.; Jacobs, W. R., Jr. Altered NADH/NAD+ ratio mediates coresistance to isoniazid and ethionamide in mycobacteria. Antimicrob. Agents Chemother. 2005, 49, 708-720.
3. Dye, C. Global epidemiology of tuberculosis. Lancet 2006, 367, 938-940.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. Vanheusden, V.; Munier-Lehmann, H.; Pochet, S.; Herdewijn, P.; Van Calenbergh, S. Synthesis and evaluation of thymidine-5′-O-mono-phosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase. Bioorg. Med. Chem. Lett. 2002, 12, 2695-2698.
10. 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.
11. Haouz, A.; Vanheusden, V.; Munier-Lehmann, H.; Froeyen, M.; Herdewijn, P.; Van Calenbergh, S.; Delarue, M. J. Enzymatic and structural analysis of inhibitors designed against M. tuberculosis thymidylate kinase: new insights into the phosphoryl transfer mechanism. Biol. Chem. 2003, 278, 4963-4971.
12. 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. Chem Bio Chem 2003, 4, 742-747.
13. Van Daele, I.; Munier-Lehmann, H.; Froeyen, M.; Balzarini, J.; Van Calenbergh, S. Rational design of 5′-thiourea-substituted a-thymidine analogues as thymidine monophosphate kinase inhibitors capable of inhibiting mycobacterial growth. J. Med. Chem. 2007, 50, 5281-5292.
14. Hopfinger, A. J.; Wang, S.; Tokarski, J. S.; Jin, B.; Albuquerque, M.; Madhav, P. J.; Duraiswami, C. Construction of 3D-QSAR models using the 4D-QSAR analysis formalism. J. Am. Chem. Soc. 1997, 119, 10509-10524.
15. Blondin, C.; Serina, L.; Wiesmü ller, 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.
16. HyperChem Program Release 7.05 for Windows; Hybercube, Inc.: Gainesville, FL, 2005.
17. Dewar, M. J. S. E.; Zoebisch, G.; Healy, E. F.; Stewart, J. J. P. AM1: A new general purpose quantum mechanical molecular model. J. Am. Chem. Soc. 1985, 107, 3902-3909.
18. Doherty, D. C. MOLSIM Package version 3.2; The Chem21 Group, Inc.: Lake Forest, IL, 2001.
19. 4D-QSAR Package version 2.0; The Chem21 Group Inc.: Lake Forest, IL, 1997.
20. Glen, W. G.; Dunn, W. J.; Scott, D. R. Principal components analysis and partial least-squares regression. Tetrahedron Comput. Methodol. 1989, 2, 349-354.
21. Rogers, D. G.; Hopfinger, A. J. Application of genetic function approximation to quantitative structure-activity relationships and quantitative structure-property relationships. J. Chem. Inf. Comput. Sci. 1994, 34, 854-866.
22. Dunn, W. J., III; Rogers D. Genetic Partial Least Squares in QSAR. In Genetic Algorithms Molecular Modeline: Devillers, J., Ed.; Academic: London, 1996; pp 109-130.
23. Friedman, J. H. Multivariate adaptative regression splines; Technical Report No. 102; Laboratory for Computational Statistics, Departament of Statistics, Stanford University: Stanford, CA, 1988.
24. Rogers, D. WOLF Genetic Function Approximation. Reference Manual, version 5.5; Molecular Simulation Inc.: Burlington, MA, 1994.
25. Rogers, D. G/SPLINES: A hybrid of Friedman's multivariate adaptative regression splines (MARS) algorithm with Holland's genetic algorithm. In The Proceedings of the Fourth International Conference on Genetic Algorithms; Belew, R. K., Booker, L. B., Eds.; Morgan Kaufmann Publishers: San Francisco, 1991; pp 38-46.
26. Mannhold, R.; van de Waterbeemd, H. Substructure and whole molecule approaches for calculating log P. J. Comput.-Aided Mol. Des. 2001, 15, 337-354.
27. Ghose, A. K.; Pritchett, A.; Crippen, G. M. Atomic physicochemical parameters for three-dimensional structure directed quantitative structure-activity relationships III: Modeling hydrophobic interactions. J. Comput. Chem. 1988, 9, 80-90.
28. Discovery Studio Visualizer version 2.0; Accelrys Software Inc.: San Diego, CA, 2007.
29. DeLano, W. L. The Pymol Molecular Graphics System version 1.0; Delano Scientific LLC: Palo Alto, CA, 2004.
30. Van Calenbergh, S. Structure-aided design of inhibitors of Mycobacterium tuberculosis thymidylate kinase. Verh K Acad. Geneeskd Bels. 2006, 68, 223-48.