Probing the anticancer activity of nucleoside analogues: A QSAR model approach using an internally consistent training set

Journal of Medicinal Chemistry

Volumn 50, Issue 7, 2007, Pages 1537-1545

  Helguera, Aliuska Morales ^a,b   Rodriguez Borges J E ^a   García Mera, Xerardo ^c   Fernández, Franco ^c   Cordeiro, M Natália D S ^a  

^a UNIVERSITY OF PORTO   (Portugal)

^b CENTRAL UNIVERSITY OF LAS VILLAS   (Cuba)

^c UNIVERSITY OF SANTIAGO DE COMPOSTELA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

NUCLEOSIDE DERIVATIVE;

ACCURACY; ANIMAL CELL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CALIBRATION; CYTOTOXICITY; DRUG SCREENING; LEUKEMIA L 1210; MODEL; NONHUMAN; PREDICTION; QUANTITATIVE STRUCTURE ACTIVITY RELATION; VALIDATION PROCESS;

ALGORITHMS; ANTINEOPLASTIC AGENTS; DATABASES, FACTUAL; DISCRIMINANT ANALYSIS; MODELS, MOLECULAR; NUCLEOSIDES; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 34147154787     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm061445m     Document Type: Article

References (76)

1. Simons, C. Carbocyclic Nucleosides; Gordon & Breach Science Publisher: Reading,UK, 2001; Vol. 3, pp 137-153.
2. Jordheim, L.; Galmarini, C. M.; Dumontet, C. Nucleoside analogues and nucleobases in cancer treatment. Lancet Oncol. 2002, 3, 415-424.
3. Jordheim, L.; Galmarini, C. M.; Dumontet, C. Drug resistance to cytotoxic nucleoside analogues. Curr. Drug Targets 2003,4 (6), 443-460.
4. Jordheim, L.; Galmarini, C. M.; Dumontet, C. Recent developments to improve the efficacy of cytotoxic nucleoside analogues. AntiCancer Drug Discovery 2006, 1, 163-170.
5. Balzarini, J.; De Clercq, E.; Torrence, P. F.; Mertes, M. P.; Park, J. S.; Schmidt, C. L.; Shugar, D.; Barr, P. J.; Jones, A. S.; Verhelst, G.; Walker, R. T. Role of thymidine kinase in the inhibitory activity of 5-substituted-2'-deoxyuridines on the growth of human and murine tumor cell lines. Biochem. Pharmacol. 1982, 31 (6), 1089-95.
6. Balzarini, J.; de Clercq, E.; Ayusawa, D.; Seno, T. Thymidylate synthetase-positive and -negative murine mammary FM3A carcinoma cells as a useful system for detecting thymidylate synthetase inhibitors. FEBS Lett 1984, 173 (1), 227-32.
7. Dixit, K. S.; Mitra, S. N. Bioinformatics in drug discovery. Curr. Res. Inf. Pharm. Sci. 2002, 3, 2-6.
8. Estrada, E.; Uriarte, E.; Montera, A.; Teijeira, M.; Santana, L.; De Clercq, E. A novel approach for the virtual screening and rational design of anticancer compounds. J. Med. Chem. 2000, 43 (10), 1975-85.
9. Gálvez, J.; García-Domenech, R.; Gómez- Lechón, M. J.; Castell, J. V. Use of molecular topology in the selection of new cytostatic drugs. J. Mol. Struct. (THEOCHEM) 2000, 504, (1-3.), 241-248.
10. Estrada, E.; Uriarte, E. Recent advances on the role of topological indices in drug discovery research. Curr. Med. Chem. 2001, 8, 1573-1588.
11. Xiao, Z.; Xiao, Y.-D.; Feng, J.; Golbraikh, A.; Tropsha, A.; Lee, K.-H. Antitumor agents. 213. Modeling of epipodophyllotoxin derivatives using variable selection k nearest neighbor QSAR method, J. Med. Chem. 2002, 45, 2294-2309.
12. Gonzalez-Diaz, H.; Gia, O.; Uriarte, E.; Hernández, I.; Ramos, R.; Chaviano, M.; Seijo, S.; Castillo, J. A.; Morales, L.; Santana, L.; Akpaloo, D.; Molina, E.; Cruz, M.; Torres, L. A.; Cabrera, M. A. Markovian chemicals "in silico" design (MARCH-INSIDE), a promising approach for computer-aided molecular design I: discovery of anticancer compounds. J. Mol. Model. (Online) 2003, 9 (6), 395-407.
13. Ren, S. S.; Lien, E. J. Anticancer agents: tumor cell growth inhibitory activity and binary QSAR analysis. Curr. Pharm. Des. 2004, 10, 1399-1415.
14. Saczewski, F.; Reszka, R.; Gdaniec, M.; Grünert, R.; Bednarski, P. J. Synthesis, X-ray crystal structures, stabilities, and in vitro cytotoxic activities of new heteroarylacrylonitriles. J. Med. Chem. 2004, 47, 3438-3449.
15. Kozikowski, A. P.; Roth, B.; Tropsha. A. Why academic drug discovery makes sense. Science 2006, 313, 1235-1236.
16. Huang, R.; Wallqvist, A.: Covell, D. G. Assessment of in vitro and in vivo activities in the National Cancer Institute's anticancer screen with respect to chemical structure, target specificity, and mechanism of action. J. Med. Chem. 2006, 23 (49), 1964-1979.
17. Verma, R. P. Understanding apoptosis in terms of QSAR. Anticancer Agents Med. Chem. 2006, 6(1), 41-52.
18. Clare, B. W.; Supuran, C. T. A perspective on quantitative structure-activity relationships and carbonic anhydrase inhibitors. Expert Opin. Drug. Metab. Toxicol. 2006, 2, 113-137.
19. Glenn, M. P.; Kahnberg, P.; Boyle, G. M.; Hansford, K. A.; Hans, D.; Martyn, A. C.; Parsons, P. G.; Fairlie, D. P. Antiproliferative and phenotype-transforming antitumor agents derived from cysteine. J. Med. Chem. 2004, 47, 2984-2994.
20. Todeschini, R.; Consonni, V. Handbook of Molecular Descriptors; Wiley VCH: Weinheim, Germany. 2000.
21. Adeel Malik, A.; Singh, H.; Andrabi, M.; Husain, S. H.; Shandar, A. Databases and QSAR for cancer research. Cancer Inf. 2006, 2, 99-111.
22. Balo, M. C.; Fernandez, F.; Lens, E.; López, C.; De Clercq, E.; Andrei, G.; Snoeck, R.; Balzarini, J. Synthesis and antiviral activities of some novel carbocyclic nucleosides. Nucleosides Nucleotides 1996, 15, (7), 1335-1346.
23. Blanco, J. M.; Caamaño, O.; Fernández, F.; Gómez, G.; Nieto, M. I.; Balzarini, J.; Padalko, E.; De Clercq, E. Synthesis and antiviral and cytostatic activities of carbocyclic nucleosides incorporating a modified cyclopentane ring. I: guanosine analogues. Nucleosides Nucleotides 1997, 16(1, 2), 159-171.
24. Nieto, M. I.; Blanco, J. M.; Caamaño, O.; Fernández, F.; García-Mera, X.; Balzarini. J.; Padalko, E.; Neytsb, J.; De Clercq, E. Synthesis, antiviral and cytostatic activities of carbocyclic nucleosides incorporating a modified cyclopentane ring. Part 2: adenosine and uridine analogues. Nucleosides Nucleotides 1998, 17, (7), 1255-1.
25. Blanco, J. M.; Caamaño, O.; Fernandez, F.; Garcia-Mera, X.; Hergueta, A. R.; Lopez, C.; Rodriguez-Borges, J. E.; Balzarini, J.; De Clercq, E. Synthesis and antiviral and antineoplastic activities of some novel carbocyclic guanosine analogues with a cyclobutane ring. Chem. Pharm. Bull. (Tokyo) 1999, 47, (9), 1314-7.
26. Figueira, M. J.; Blanco, J. M.; Caamaño, O.; Fernández, F.; García-Mera, X.; López, C.; Andrei, G.; Snoeck, R.; Padalko, E.: Neyts, J.; Balzarini, J.; De Clercq, E. Synthesis and antiviral and cytostatic activities of carbocyclic nucleosides incorporating a modified cyclobutane ring. Part 1. Guanosine analogues. Archiv der Pharmazie 1999, 332, 348-352.
27. López, C.; Balo, C.; Blanco, J. M.; Fernández, F.; De Clercq, E.: Balzarini, J. A cyclobutane carbonucleoside with marked selectivity against tk+ and tk- varicella zoster virus Nucleosides Nucleotides 2001, 20 (4, 7), 1133-1135.
28. Figueira, M. J.; Caamaño, O.; Fernández, F.; Blanco, J. M. Synthesis of (6)-c-4-amino-r-1,t-2,c-3-cyclopentanetrimethanol and higher homologues of 8-azapurine arabino-carbocyclic nucleosides. Tetrahedron 2002, 58, 7233-7240.
29. Yao, S. W.; Lopes, V. H.; Fernandez, F.; Garcia-Mera, X.; Morales, M.; Rodriguez-Borges, J. E.; Cordeiro, M. N. Synthesis and QSAR study of the anticancer activity of some novel indane carbocyclic nucleosides. Bioorg. Med. Chem. 2003, 11 (23), 4999-5006.
30. Fernández, F.; García-Mera, X.; Morales, M.; Vilariño, L.; Caamaño, O.; De Clercq, E. Synthesis of new 6-substituted purinyl-5′-nor-1′-homocarbanucleosides based on indanol. Tetrahedron 2004, 60, 9245-9253.
31. Caamaño, O.; Gómez, G.; Fernández, F.; García, M. D.; García-Mera, X.; De Clercq, E. A Convenient Synthesis of New Purinyl-homo-carbonucleosides on a Cyclopentane Ring Fused with Pyridazine. Synthesis 2004, 17, 2855-2862.
32. Fernández, F.; García-Mera, X.; López, C.; Morales, M.; Rodríguez-Borges, J. E. A Convenient Synthesis of Novel Pyrimidinyl-5′-nor-1′-homocarbanucleosides Based on Indanol. Synthesis 2005, 20, 3549-3554.
33. Nieto, M.; Caamaño, O.; Fernández, F.: Gómez, M.: Balzarini, J.; De Clercq, E. Synthesis, antiviral and cytostatic activities, of carbocyclic nucleosides incorporating a modified cyclopentane ring. Part 4: adenosine and uridine analogues. Nucleosides, Nucleotides Nucleic Acids 2002, 21 (3), 243-255.
34. Figueira, M. J.; Caamaño, O.; Fernandez, F.: Rodriguez-Borges, J. E.; Balzarini, J.; De Clercq, E. Synthesis and Biological Evaluation of Carbocyclic Nucleosides with 2′,3′-Dihomo-xylo-carbocyclic or Carbocyclic Fused to a Tetrahydrofuran Ring. Synthesis 2004, 12, 1991-1995.
35. Hergueta, A. R.; Fernandez, F.; Lopez, C.; Balzarini, J.; De Clercq, E. Novel carbocyclic nucleosides containing a cyclobutyl ring: adenosine analogues. Chem. Pharm. Bull. (Tokyo) 2001, 49 (9), 1174-7.
36. Balo, C.; Fernández, F.; Lens, E.; López, C.; Andrei, G.; Snoeck, R.; Balzarini, J.; De Clercq. E. Novel carbocyclic nucleosides containing a cyclopentyl ring. Adenosine and uridine analogues. Archiv der Pharmazie 1997, 330, 265-267.
37. Blanco, J. M.; Caamaño, O.; Fernandez, F.; Rodriguez-Borges, J. E.; Balzarini, J.; de Clercq, E. Carbocyclic analogues of nucleosides from bis-(Hydroxymethyl)-cyclopentane: synthesis, antiviral and cytostatic activities of adenosine, inosine and uridine analogues. Chem. Pharm. Bull. (Tokyo) 2003, 51, (9), 1060-3.
38. Wnuk, S. F.; Yuan, C. S.; Borchardt, R. T.; Balzarini, J.; De Clercq, E.; Robins, M. J. Anticancer and antiviral effects and inactivation of S-adenosyl-L-homocysteine hydrolase with 5′- carboxaldehydes and oximes synthesized from adenosine and sugar-modified analogues. J. Med. Chem. 1997, 40 (11), 1608-18.
39. Gonzalez-Diaz, H.; Viña, D.; Santana, L.; de Clercq, E.; Uriarte, E. Stochastic entropy QSAR for the in silico discovery of anticancer compounds: prediction, synthesis, and in vitro assay of new purine carbanucleosides. Bioorg. Med. Chem. 2006, 14 (4), 1095-107.
40. Prekupec, S.; Svedruzic, D.; Gazivoda, T.; Mrvos-Sermek, D.; Nagl, A.; Grdisa, M.; Pavelic, K.; Balzarini, J.; De Clercq, E.; Folkers, G.; Scapozza, L.; Mintas, M.; Raic-Malic, S. Synthesis and biological evaluation of iodinated and fluorinated 9-(2-hydroxypropyl) and 9-(2-hydroxyethoxy)methyl purine nucleoside analogues. J. Med. Chem. 2003, 46 (26), 5763-72.
41. Moosavi-Movahedi, A. A.; Hakimelahi, S.; Chamani, J.; Khodarahmi, G. A.; Hassanzadeh, F.; Luo, F. T.; Ly, T. W.; Shia, K. S.; Yen, C. F.; Jain, M. L.; Kulatheeswaran, R.; Xue, C.; Pasdar, M.; Hakimelahi, G. H. Design, synthesis, and anticancer activity of phosphonic acid diphosphate derivative of adenine-containing butenolide and its water-soluble derivatives of paclitaxel with high antitumor activity. Bioorg. Med. Chem. 2003, 11 (20), 4303-13.
42. Raic-Malic, S.; Svedruzic, D.; Gazivoda, T.; Marunovic, A.; Hergold-Brundic, A.; Nagl, A.; Balzarini, J.; De Clercq, E.; Mintas, M. Synthesis and antitumor activities of novel pyrimidine derivatives of 2,3-O,O-dibenzyl-6-deoxy-L-ascorbic acid and 4,5-didehydro-5,6-dideoxy-L-ascorbic acid. J. Med. Chem. 2000, 43, (25), 4806-11.
43. Santana, L.; Teijeira, M.; Uriarte, E.; Balzarini, J.; De Clercq, E. Synthesis, conformational analysis and antiviral and antitumoral activity of new 1,2-disubstituted carbocyclic nucleosides. Eur. J. Med. Chem. 2002, 37 (9), 755-60.
44. Hakimelahi, G. H.; Mei, N. W.; Moosavi-Movahedi, A. A.; Davari, H.; Hakimelahi, S.; King, K. Y.; Hwu, J. R.; Wen, Y. S. Synthesis and biological evaluation of purine-containing butenolides. J. Med. Chem. 2001, 44 (11), 1749-57.
45. Hakimelahi, G. H., Moosavi-Movahedi, A. A.; Sambaiah, T.; Zhu, J. L.; Ethiraj, K. S.; Pasdar, M.; Hakimelahi, S. Reactions of purines-containing butenolides with L-cysteine or N-acetyl-L-cysteine as model biological nucleophiles: a potent mechanism-based inhibitor of ribonucleotide reductase caused apoptosis in breast carcinoma MCF7 cells. Eur. J. Med. Chem. 2002, 37 (3), 207-17.
46. Hatse, S.; Naesens, L.; De Clercq, E.; Balzarini, J. N6-cyclopropyl- PMEDAP: a novel derivative of 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP) with distinct metabolic, antiproliferative, and differentiation- inducing properties. Biochem. Pharmacol. 1999, 58(2), 311-23.
47. Teran, C.; Santana, L.; Teijeira, M.; Uriarte, E.; De Clercq, E. Design, synthesis, conformational analysis and biological activities of purine-based 1,2-di-substituted carbocyclic nucleosides. Chem. Pharm. Bull. (Tokyo) 2000, 48 (2), 293-5.
48. Wang, Z. X.; Wiebe, L. I.; Balzarini, J.; De Clercq. E.; Knaus, E. E. Chiral synthesis of 4-[l-(2-deoxy-beta-L-ribofuranosyl)] derivatives of 2-substituted 5-fluoroaniline: "cytosine replacement" analogues of deoxy-beta-L-cytidine. J. Org. Chem. 2000, 65 (26), 9214-9.
49. Wnuk, S. F.; Yuan, C. S.; Borchardt, R. T.; Balzarini, J.; De Clercq, E.; Robins, M. J. Nucleic acid related compounds. 84. Synthesis of 6′-(E and Z)-halohomovinyl derivatives of adenosine, inactivation of S-adenosyl-L-homocysteine hydrolase, and correlation of anticancer and antiviral potencies with enzyme inhibition. J. Med. Chem. 1994, 37(21), 3579-87.
50. Kundu, N. G.; Das, P.; Balzarini, J.; De Clercq, E. Palladium-catalyzed synthesis of [E]-6-(2-acylvinyl)uracils and [E]-6-(2-acylvinyl)-1 -[(2-hydroxyethoxy)methyl]uracils-their antiviral and cytotoxic activities. Bioorg. Med. Chem. 1997, 5 (11), 2011-8.
51. Mikhailopulo, I. A.; Poopeiko, N. E.; Pricota, T. I.; Sivets, G. G.; Kvasyuk, E. I.; Balzarini, J.; De Clercq, E. Synthesis and antiviral and cytostatic properties of 3′-deoxy-3′-fluoro- and 2′-azido-3′-fluoro-2′,3′-dideoxy-D-ribofuranosides of natural heterocyclic bases. J. Med. Chem. 1991, 34 (7), 2195-202.
52. Raic-Malic, S.; Hergold-Brundic, A.; Nagl, A.; Grdisa, M.: Pavelic, K.; De Clercq, E.; Mintas, M. Novel pyrimidine and purine derivatives of L-ascorbic acid: synthesis and biological evaluation. J. Med. Chem. 1999, 42 (14), 2673-8.
53. De Clercq, E.; Balzarini, J.; Torrence, P. F.; Merles, M. P.; Schmidt, C. L.; Shugar, D.; Barr, P. J.; Jones, A. S.; Verhelst, G.; Walker, R. T. Thymidylate synthetase as target enzyme for the inhibitory activity of 5-substituted 2′-deoxyuridines on mouse leukemia L1210 cell growth. Mol. Pharm. 1981, 19 (2), 321-30.
54. De Clercq, E.; Descamps, J.; Balzarini, J.; Giziewicz, J.; Barr, P. J.; Robins, M. J. Nucleic acid related compounds. 40. Synthesis and biological activities of 5-alkynyluracil nucleosides. J. Med. Chem. 1983, 20 (5), 661-6.
55. Robins, M. J.; Hatfield, P. W.; Balzarini, J.; De Clercq, E. Nucleic acid related compounds. 47. Synthesis and biological activities of pyrimidine and purine "acyclic" nucleoside analogues. J. Med. Chem. 1984, 27 (11), 1486-92.
56. Hunston, R. N.; Jones, A. S.; McGuigan, C.; Walker, R. T.; Balzarini, J.; De Clercq, E. Synthesis and biological properties of some cyclic phosphotriesters derived from 2′-deoxy-5-fluorouridine. J. Med. Chem. 1984, 27 (4), 440-4.
57. Al-Razzak, L. A.; Schwepler, D.; Decedue, C. J.; Balzarini, J.; De Clercq, E.; Mertes, M. P. 5-Quinone derivatives of 2′-deoxyuridine 5′-phosphate: inhibition and inactivation of thymidylate synthase, antitumor cell, and antiviral studies. J. Med. Chem. 1987, 30 (2), 409-19.
58. Bobek, M.; An, S. H.; Skrincosky, D.; De Clercq, E.; Bernacki, R. J. 2′-Fluorinated isonucleosides. 1. Synthesis and biological activity of some methyl 2′-deoxy-2′-fluoro-2′-pyrimidinyl-D- arabinopyranosides. J. Med. Chem. 1989, 32 (4), 799-807.
59. Pestana, M.; Gageiro, J., Análise de dados para Ciências Sociais. A Complementaridade do SPSS: 2nd ed.; Ediçoes Sílabo: Lisboa, 2000; p 570.
60. Provost, F.; Fawcett, T. In Analysts and visualization of classifier performance comparison under class and cost distributions, Third International Conference on Knowledge Discovery and Data Mining (KDD-97). 1997; American Association for Artificial Intelligence Press: 1997.
61. Toivonen, H.; Srinivasan, A.; King, R. D.; Kramer, S.; Helma, C. Statistical evaluation of the Predictive Toxicology Challenge 2000-2001. Bioinformatics 2003, 19 (10), 1183-93.
62. Benigni, R.; Giuliani, A. Putting the Predictive Toxicology Challenge into perspective: reflections on the results. Bioinformatics 2003, 19 (10), 1194-200.
63. Randić, M.; Wilkins, C. L. Graph Theoretical Approach to Recognition of Structural Similarity in Molecules. J. Chem. Inf. Comput. Sci. 1979, 19(1), 31-37.
64. Randić, M. On Characterization of Cyclic Structures. J. Chem. Inf. Comput. Sci. 1997, 37, 1063-1071.
65. Golbraikh, A.; Tropsha, A. Beware of q2! J. Mol. Graph. Model. 2002, 20 (4), 269-76.
66. Golbraikh, A.; Shen, M.; Xiao, Z.; Xiao, Y. D.; Lee, K. H.; Tropsha, A. Rational selection of training and test sets for the development of validated QSAR models. J. Comput.-Aided Mol. Des. 2003, 17 (2-4), 241-53.
67. Golbraikh, A.; Tropsha, A. Predictive QSAR modeling based on diversity sampling of experimental datasets for the training and test set selection. J. Comput.-Aided Mol. Des. 2002, 16 (5-6), 357-69.
68. Todeschini, R.; Consonni, V.; Pavan, M. Dragon Software, version 2.1; 2002.
69. Statsoft, I. STATISTICA (data analysis software system), version 6.0: 2002.
70. Selwood, D. L.; Livingstone, D. J.; Comley, J. C. W.; O'Dowd, A. B.; Hudson, A. T.; Jackson, P.; Pandu, K. S. Structure-activity relationships of antifilarial antimycin analogues: a multivariate pattern recognition study. J. Med. Chem. 1990, 33, 136-142.
71. Randić, M. Correlation of enthalphy of octanes with orthogonal connectivity indices. J. Mol. Struct. (THEOCHEM) 1991, 233, 45-59.
72. Randić, M. Orthogonal Molecular Descriptors. New J. Chem. 1991, 15 (7), 517-525.
73. Randić, M. Resolution of Ambiguities in Structure-Property Studies by Use of Orthogonal Descriptors. J. Chem. Inf. Comput. Sci. 1991, 31, 311-320.
74. Peterangelo, S. C.; Seybold, P. G. Synergistic interactions among QSAR descriptors. Int. J. Quant. Chem. 2004, 96, 1-9.
75. Osborne, J.; Waters, E. Four assumptions of multiple regression that researchers should always test. Pract. Assess. Res. Eval. 2002, 8, 2.
76. Van Waterbeemd, H. Chemometric Methods in Molecular Design. In Method and Principles in Medicinal Chemistry; Manhnhold, R.; Krogsgaard-Larsen, R.; Timmerman, H., Eds.; VCH: Weinheim. 1995; Vol. 2, pp 265-282.