Design, synthesis, and biological evaluation of fluoronitrophenyl substituted folate analogues as potential inhibitors of GAR transformylase and AICAR transformylase

Bioorganic and Medicinal Chemistry Letters

Volumn 10, Issue 13, 2000, Pages 1471-1475

  Boger, Dale L ^a   Marsilje, Thomas H ^a   Castro, René A ^a   Hedrick, Michael P ^a   Jin, Qing ^a   Baker, Stephen J ^b   Shim, Jae Hoon ^b   Benkovic, Stephen J ^b  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b PENNSYLVANIA STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ENZYME INHIBITOR; FOLIC ACID DERIVATIVE; LOMETREXOL; PHOSPHORIBOSYLAMINOIMIDAZOLECARBOXAMIDE FORMYLTRANSFERASE; PHOSPHORIBOSYLGLYCINAMIDE FORMYLTRANSFERASE; PHOSPHORIBOSYLGLYCINAMIDE FORMYLTRANSFERASE INHIBITOR;

ARTICLE; CHEMICAL REACTION; CYTOTOXICITY; DRUG DESIGN; DRUG INHIBITION; DRUG SYNTHESIS; HUMAN; HUMAN CELL; STRUCTURE ANALYSIS;

ANIMALS; BIOLOGICAL ASSAY; COMBINATORIAL CHEMISTRY TECHNIQUES; DRUG DESIGN; ENZYME INHIBITORS; FLUORINE; FOLIC ACID; HYDROXYMETHYL AND FORMYL TRANSFERASES; LEUKEMIA, LYMPHOCYTIC, ACUTE; MOLECULAR STRUCTURE; NITRO COMPOUNDS; PHOSPHORIBOSYLGLYCINAMIDE FORMYLTRANSFERASE; PURINES; RIBONUCLEOTIDES; TUMOR CELLS, CULTURED;

EID: 0034601253     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(00)00271-7     Document Type: Article

References (31)

1. Warren M.S., Mattia K.M., Marolewski A.E., Benkovic S.J. Pure Appl. Chem. 68:1996;2029.
2. Jackson, R. C.; Harkrader, R. J. In Nucleosides and Cancer Treatment; Tattersall, M. H. N., Fox, R. M., Eds.; Academic: Sydney, 1981; pp 18-31.
3. (a) Beardsley, G. P.; Moroson, B. A.; Taylor, E. C.; Moran, R. G. J. Biol. Chem. 1989, 264, 328.
4. (b) Baldwin, S. W.; Tse, A.; Gossett, L. S.; Taylor, E. C.; Rosowsky, A.; Shih, C.; Moran, R. G. Biochemistry 1991, 30, 1997.
5. (a) Boger, D. L.; Haynes, N.-E.; Kitos, P. A.; Warren, M. S.; Ramcharan, J.; Marolewski, A. E.; Benkovic, S. J. Bioorg. Med. Chem. 1997, 5, 1817.
6. (b) Boger, D. L.; Haynes, N.-E.; Warren, M. S.; Gooljarsingh, L. T.; Ramcharan, J.; Kitos, P. A.; Marolewski, A. E.; Benkovic, S. J. Bioorg. Med. Chem. 1997, 5, 1831.
7. (c) Boger, D. L.; Haynes, N.-E.; Warren, M. S.; Ramcharan, J.; Kitos, P. A.; Benkovic, S. J. Bioorg. Med. Chem. 1997, 5, 1839.
8. (d) Boger, D. L.; Haynes, N.-E.; Warren, M. S.; Ramcharan, J.; Marolewski, A. E.; Kitos, P. A.; Benkovic, S. J. Bioorg. Med. Chem. 1997, 5, 1847.
9. (e) Boger, D. L.; Kochanny, M. J.; Cai, H.; Wyatt, D.; Kitos, P. A.; Warren, M. S.; Ramcharan, L. T.; Gooljarsingh, L. T.; Benkovic, S. J. Bioorg. Med. Chem. 1998, 6, 643.
10. Terrier, F. In Nucleophilic Aromatic Displacement: The Influence of the Nitro Group; VCH: New York, 1991.
11. Boger D.L., Zhou J., Borzilleri R.M., Nukui S., Castle S.L. J. Org. Chem. 62:1997;2059.
12. (a) Sanger, F. Biochem. J. 1945, 39, 507.
13. (b) Zahn, H. Kolloid-Z. 1951, 121, 40.
14. (c) Zahn, H.; Meienhofer, J. Makromol. Chem. 1958, 26, 126.
15. (a) Molina, H. A.; Bistoletti, Y. Acta Bioquim. Clin. Latinoam. 1988, 22, 391.
16. (b) Shanahan, M. F.; Jacquez, J. A. Membr. Biochem. 1978, 1, 239.
17. (c) Riva, F.; Giantoso, A.; Voltattorni, C. B.; Turano, C. Methods Enzymol. 1979, 62, 510.
18. (d) Riva, F.; Giartosio, A.; Turano, C. Methods Enzymol. 1977, 46, 441.
19. (e) Riva, F.; Giartosio, A.; Voltattorni, C. B.; Orlacchio, A.; Turano, C. Biochem. Biophys. Res. Commun. 1975, 66, 863.
20. (f) Riva, F.; Carotti, D.; Barra, D.; Giartosio, A.; Turano, C. J. Biol. Chem. 1980, 255, 9230.
21. (g) Carotti, D.; Riva, F.; Santucci, R.; Ascoli, F.; Fasella, P. Eur. J. Biochem. 1982, 124, 589.
22. (h) Ottonello, S.; Mozzarelli, A.; Rossi, G. L.; Carotti, D.; Riva, F. Eur. J. Biochem. 1983, 133, 47.
23. (i) Carotti, D.; Andria, F.; Giartosio, A.; Turano, C.; Riva, F. Eur. J. Biochem. 1985, 146, 619.
24. (a) Taylor, E. C.; Harrington, P.M.; Shih, C. A. Heterocycles 1989, 28, 1169.
25. (b) Shih, C.; Gossett, L. S.; Worzalla, J. F.; Rinzel, S. M.; Grindey, G. B.; Harrington, P. M.; Taylor, E. C. J. Med. Chem. 1992, 35, 1109.
26. (c) Bigham, E. C.; Hodson, S. J.; Mallory, R.; Wilson, D.; Duch, D. S.; Smith, G. K.; Ferone, R. J. Med. Chem. 1992, 35, 1399.
27. (d) Taylor, E. C.; Schrader, T. H.; Walensky, L. D. Tetrahedron 1992, 48, 19.
28. (a) Jacobson, A. R.; Tam, S. W.; Sayre, L. M. J. Med. Chem. 1991, 34, 2816.
29. (b) Khan, H. A.; Robins, D. J. J. Chem. Soc. Perkin Trans. 1 1985, 101.
30. 6, 250 MHz) δ 8.56 (d, J=8.4 Hz, 1H), 7.84 (d, J=9.1 Hz, 2H), 7.38 (d, J=8.0 Hz, 2H), 7.31 (d, J=15.0 Hz, 1H), 4.73 (s, 2H), 4.46-4.32 (m, 1H), 3.29-3.15 (m, 2H), 2.34 (t, J=8.0 Hz, 2H), 2.20-2.05 (m, 2H), 2.03-1.88 (m, 2H), 1.74-1.60 (m, 2H).
31. The CCRF-CEM cytotoxicity assay, the AICAR Tfase inhibition studies and the time-dependent GAR Tfase inhibition studies were performed as described in Boger, D. L.; Haynes, N.-E.; Kitos, P. A.; Warren, M. S.; Ramcharan, J.; Marolewski, A. E.; Benkovic, S. J. Bioorg. Med. Chem. 1997, 5, 1817 with the following changes: In the GAR Tfase assay, solutions were made containing 50 nM purN GAR Tfase, 750 nM BSA, 1.25 mM GAR (if GAR was present during the pre-incubation) and 250 μM inhibitor. These solutions were incubated at room temperature. Aliquots of these stock solutions were taken, diluted 25-fold in assay buffer, and thermostated to 26 °C on a Cary 1 UV-Visible spectrophotometer. Assays were initiated by the addition of 20 μM fDDF at the indicated time points. In the AICAR Tfase assay, the assay solutions were incubated at room temperature for 12 h before the reaction was initiated by addition of AICAR.