Synthesis and biological activity of folic acid and methotrexate analogues containing L-threo-(2S,4S)-4-fluoroglutamic acid and DL-3,3-difluoroglutamic acid

Journal of Medicinal Chemistry

Volumn 39, Issue 1, 1996, Pages 56-65

  Hart, Barry P ^a   Haile, William H ^b   Licato, Nicholas J ^a   Bolanowska, Wanda E ^b   McGuire, John J ^b   Coward, James K ^a  

^a UNIVERSITY OF MICHIGAN   (United States)

^b ROSWELL PARK CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3,3 DIFLUOROGLUTAMIC ACID; 4 FLUOROGLUTAMIC ACID; BETA,BETA DIFLUOROFOLIC ACID; DIHYDROFOLATE REDUCTASE; FOLIC ACID; GAMMA FLUOROFOLIC ACID; GAMMA FLUOROMETHOTREXATE; METHOTREXATE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG ACTIVITY; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; LEUKEMIA CELL; NUCLEAR MAGNETIC RESONANCE; STEREOSPECIFICITY;

ANIMALS; FOLIC ACID; FOLIC ACID ANTAGONISTS; GLUTAMATES; HUMANS; KINETICS; MAGNETIC RESONANCE SPECTROSCOPY; METHOTREXATE; MOLECULAR STRUCTURE; PEPTIDE SYNTHASES; PTEROYLPOLYGLUTAMIC ACIDS; RATS; STEREOISOMERISM; TETRAHYDROFOLATE DEHYDROGENASE; TUMOR CELLS, CULTURED;

EID: 0030026396     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm950515e     Document Type: Article

References (44)

1. McGuire, J. J.; Coward, J. K. In Folates and Pterins; Blakley, R. L., Benkovic, S. J., Eds.; John Wiley & Sons: New York, 1984; Vol. 1, pp 135-190.
2. Matherly, L. H.; Seither, R. L.; Goldman, I. D. Metabolism of the diaminoantifolates: Biosynthesis and pharmacology of the 7-hydroxyl and polyglutamyl metabolites of methotrexate and related antifolates. Pharmacol. Ther. 1987, 35, 27-56.
3. McGuire, J. J.; Coward, J. K. DL-threo-4-Fluoroglutamic acid: A chain terminating inhibitor of folylpolyglutamate synthetase. J. Biol. Chem. 1985, 260, 6747-6754.
4. McGuire, J. J.; Haile, W. H.; Bey, P.; Coward, J. K. DL-3,3-Difluoroglutamate: An enhancer of folylpolyglutamate elongation. J. Biol. Chem. 1990, 265, 14073-14079.
5. McGuire, J. J.; Graber, M.; Licato, N.; Vincenz, C.; Coward, J. K.; Nimec, Z.; Galivan, J. Biochemical and growth inhibitory effects of the erythro and threo isomers of γ-fluoromethotrexate, a methotrexate analogue defective in polyglutamylation. Cancer Res. 1989, 49, 4517-4525.
6. McGuire, J. J.; Hart, B. P.; Haile, W. H.; Rhee, M.; Galivan, J.; Coward, J. K. DL-β,β-Difluoroglutamic acid mediates position-dependent enhancement or termination of pteroylpoly (γ-glutamate) synthesis catalyzed by folylpolyglutamate synthetase. Arch. Biochem. Biophys. 1995, 321, 319-328.
7. Galivan, J.; Inglese, J.; McGuire, J. J.; Nimec, Z.; Coward, J. K. γ-Fluoromethotrexate: Synthesis and biological activity of a potent inhibitor of dihydrofolate reductase with greatly diminished ability to form poly-γ-glutamates. Proc. Natl. Acad. Sci., U.S.A. 1985, 82, 2598-2602.
8. McGuire, J. J.; Haile, W. H.; Coward, J. K. Interaction of DL-erythro- and DL-threo-γ-fluoromethotrexate with human leukemia cell dihydrofolate reductase. Biochem. Pharmacol. 1989, 38, 4321-4325.
9. 2-Glu) for glutamate (Glu). Proc. Am. Assoc. Cancer Res. 1994, 35, 302.
10. Bertino, J. R. "Rescue" techniques in cancer chemotherapy: Use of leucovorin and other rescue agents after methotrexate treatment. Seminars Oncol. 1977, 4, 203-216.
11. The Expanding Role of Folates and Fluoropyrimidines in Cancer Chemotherapy; Rustum, Y., McGuire, J. J., Eds.; Plenum Press: New York, 1988; Advances in Experimental Medicine and Biology, Vol. 244.
12. Buchanan, R. L.; Dean, F. H.; Pattison, F. L. M. γ-Fluoroglutamic acid. Can. J. Chem. 1962, 40, 1571-1575.
13. Cramer, S. M.; Schornagel, J. H.; Kalghatgi, K. K.; Bertino, J. R.; Horvath, C. Occurrence and significance of D-methotrexate as a contaminant of commercial methotrexate. Cancer Res. 1984, 44, 1843-1846.
14. McGuire, J. J.; Bolanowska, W. E.; Coward, J. K.; Sherwood, R. F.; Russell, C. A.; Felschow, D. M. Biochemical and biological properties of methotrexate analogs containing D-glutamic acid or D-erythro,threo-4-fluoroglutamic acid. Biochem. Pharmacol. 1991, 42, 2400-2403.
15. During the course of this research, a communication appeared which described the stereospecific synthesis of 5t; Hudlicky, M.; Merola, J. S. Tetrahedron Lett. 1990, 31, 7403-7406. We thank Professor Hudlicky for providing details on the synthetic route, which we had also investigated independently, and for an authentic sample of 5t.
16. Hart, B. P.; Coward, J. K. The synthesis of DL-3,3-difluoroglutamic acid from a 3-oxoprolinol derivative. Tetrahedron Lett. 1993, 34, 4917-4920.
17. Coward, J. K.; McGuire, J. J.; Galivan, J. In Selective Fluorination in Organic and Bioorganic Chemistry; Welch, J. T., Ed.; American Chemical Society: Washington, D.C., 1991; pp 196-204.
18. Rosowsky, A. Chemistry and Biological Activity of Antifolates. Prog. Med. Chem. 1989, 26, 1-252.
19. Hudlicky, M. Stereospecific syntheses of all four stereoisomers of 4-fluoroglutamic acid. J. Fluorine Chem. 1993, 60, 193-210.
20. Balinska, M.; Galivan, J.; Coward, J. K. Efflux of Methotrexate and Its Polyglutamate Derivatives from Hepatic Cells In Vitro. Cancer Res. 1981, 41, 2751-2756.
21. Licato, N. J.; Coward, J. K.; Nimec, Z.; Galivan, J.; Bolanowska, W. E.; McGuire, J. J. Synthesis of N-[N-(4-deoxy-4-amino-10-methylpteroyl)-4-fluoroglutamyl]-γ-glutamate, an unusual substrate for folylpoly-γ-glutamate synthetase and γ-glutamyl hydrolase. J. Med. Chem. 1990, 33, 1022-1027.
22. 1. J. Biol. Chem. 1971, 246, 7207-7213.
23. Hudlicky, M.; Merola, J. S. New stereospecific syntheses and X-ray diffraction structures of (-)-D-erythro- and (+)-L-threo-4-fluoroglutamic acid. Tetrahedron Lett. 1990, 31, 7403-7406.
24. 2 from Pseudomonas sp. strain RS-16. Use of a novel triazine dye affinity method. Eur. J. Biochem. 1985, 148, 447-453.
25. Huang, S. L.; Omura, K.; Swern, D. Oxidation of Sterically Hindered Alcohols to Carbonyls with Dimethyl Sulfoxide-Trifluoroacetic Anhydride. J. Org. Chem. 1976, 41, 3329-3331.
26. Yoshifuji, S.; Tanaka, K.; Kawai, T.; Nitta, Y. Chem. Pharm. Bull. 1986, 34, 3873-3878.
27. Hart, B. P. Ph.D. Thesis, The University of Michigan, Ann Arbor, May 1995.
28. Werkheiser, W. C. Specific binding of 4-amino folic acid analogues by folic acid reductase. J. Biol. Chem. 1961, 236, 888-893.
29. Delcamp, T. J.; Susten, S. S.; Blankenship, D. T.; Freisheim, J. H. Purification and characterization of dihydrofolate reductase from methotrexate-resistant human lymphoid cells. Biochemistry 1983, 22, 633-639.
30. Bergmann, E. D.; Chun-Hsu, L. Organic fluorine compounds; Part XLVI. γ-Fluoroglutamic acid and fluorofolic acid. Synthesis 1973, 1, 44-46.
31. Shane, B. Pteroylpoly(γ-glutamate) Synthesis by Corynebacterium Species. Studies on the Mechanism of Folylpoly(γ-glutamate) Synthetase. J. Biol. Chem. 1980, 255, 5663-5667.
32. Cichowicz, D. J.; Shane, B. Mammalian Folylpoly-γ-glutamate Synthetase. 2. Substrate Specificity and Kinetic Properties. Biochemistry 1987, 26, 513-521.
33. Temple, J., C.; Montgomery, J. A. In Folates and Pterins; Blakley, R. L. Benkovic, S. J., Eds.; John Wiley & Sons: New York. 1984; Vol. 1, pp 61-120.
34. Hayman, R.; McGready, R.; Van der Weyden, M. B. A rapid radiometric assay for dihydrofolate reductase. Anal. Biochem. 1978, 87, 460-465.
35. Tang, K.-C.; Coward, J. K. Synthesis of keto phosphonate analogs of biologically important acyl phosphates. J. Org. Chem. 1983, 48, 5001-5006.
36. Tamaru, Y.; Kawamura, S.-I.; Bando, T.; Tanaka, K.; Hojo, M.; Yoshida, Z.-C. Stereoselective intramolecular haloamidation of N-protected 3-hydroxy-4-pentenylamines and 4-hydroxy-5-hexenylamines. J. Org. Chem. 1988, 53, 5491-5501.
37. Nimec, Z.; Galivan, J. Regulatory aspects of the glutamylation of methotrexate in cultured hepatoma cells. Arch. Biochem. Biophys. 1983, 226, 671-680.
38. Foley, G. F.; Lazarus, H.; Farber, S.; Uzman, B. G.; Boone, B. A.; McCarthy, R. E. Continuous culture of lymphoblasts from peripheral blood of a child with acute leukemia. Cancer 1965, 18, 522-529.
39. McCloskey, D. E.; McGuire, J. J.; Russell, C. A.; Rowan, B. G.; Bertino, J. R.; Pizzorno, G.; Mini, E. Decreased folylpolyglutamate Synthetase activity as a mechanism of methotrexate resistance in CCRF-CEM human leukemia sublins. J. Biol. Chem. 1991, 266, 6181-6187.
40. McGuire, J. J.; Hsieh, P.; Coward, J. K.; Bertino, J. R. Enzymatic synthesis of folylpolyglutamates. Characterization of the reaction and its products. J. Biol. Chem. 1980, 255, 5776-5788.
41. McGuire, J. J.; Russell, C. A.; Bolanowska, W. E.; Freitag, C. M.; Jones, C. S.; Kalman, T. I. Biochemical and growth inhibition studies of methotrexate and aminopterin analogues containing a tetrazole ring in place of the γ-carboxyl group. Cancer Res. 1990, 50, 1726-1731.
42. McGuire, J. J.; Bergoltz, V. V.; Heitzman, K J.; Haile, W. H.; Russell, C. A.; Bolanowska, W. E.; Kotake, Y.; Haneda, T.; Nomura, H. Novel 6,5-fused-ring heterocyclic antifolates: Biochemical and biological characterization. Cancer Res. 1994, 54. 2673-2679.
43. McGuire, J. J.; Hsieh, P.; Coward, J. K.; Bertino, J. R. In vitro methotrexate polyglutamate synthesis by rat liver folylpolyglutamate synthetase and inhibition by faromosulfophthalein. Adv. Exp. Med. Biol. 1983, 163, 199-214.
44. Bolanowska, W. E.; Russell, C. A.; MeGuire, J. J. Activation of mammalian folylpolyglutamate synthetase by sodium bicarbonate. Arch. Biochem. Biophys. 1990, 281, 198-203.