Abstract
The compound 5,8-dideazaisofolic acid (IAHQ), 1a, was found to posses modest antitumor activity against a variety of human and murine tumor cells both in vitro and in vivo. 1–5 Its lack of potency was attributed to slow influx into target cells as demonstrated with [3H] IAHQ in the presence of HCT-8 human colon adenocarcinoma cells in culture.6 The analogues 2-desamino-5,8-dideazaisofolic acid, 1b, and 2-desamino-2-methyl-5,8-dideazaisofolic acid, 1c, were prepared subsequently and found to be 6-and 44-fold more cytotoxic toward L1210 cells than 1a 7,8 This activity enhancement correlated well with increased affinity for the reduced folate transporter as measured by competition for the uptake of [3H] MTX into MOLT-4 cells.8
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References
J.B. Hynes, Y.C.S. Yang, J.E. McGill, S.J. Harmon, and W.L. Washtien, J. Med. Chem. 27:232 (1984).
D.J. Fernandes, J.R, Bertino, and J.B. Hynes, Cancer Res. 43:1117 (1983).
J.B. Hynes, A.B. Smith, and G.R. Gale, Cancer Chemother. Pharmacol. 18:231 (1986).
K.-Y. Tsang, J.B. Hynes, and H.H. Fudenberg, Chemother. 28:276 (1982).
J.J. McGuire, A.F. Sobrero, J.B. Hynes, and J.R. Bertino, Cancer Res. 47:5975 (1987).
A.F. Sobrero, J.J. McGuire, and J.R. Bertino, Biochem. Pharmacol. 37:997 (1988).
J.B. Hynes, S.A. Patil, R.L. Hagan, A. Cole, W. Kohler, and J.H. Freisheim, J. Med. Chem. 32:852 (1989).
R. L. Hagan, D.S. Duch, G.K. Smith, M.H. Hanlon, B. Shane, J.H. Freisheim, and J.B. Hynes, Biochem. Pharmacol. 41:781 (1991).
D.J. Cichowicz and B. Shane, Biochemistry 27:504(1987).
D.J. Cichowicz, J. B. Hynes, and B. Shane, Biochem. Biophys. Acta 957:363 (1988).
J.I. McCormick, S.S. Susten, and J.H. Freisheim, Arch. Biochem. Biophys. 212:311 (1981).
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Hynes, J.B., Hagan, R.L., Shane, B., Freisheim, J.H. (1993). Synthesis and Biological Evaluation of Analogues of 5,8-Dideazaisofolic Acid (IAHQ) Modified at Positions 2, 4 and 9. In: Ayling, J.E., Nair, M.G., Baugh, C.M. (eds) Chemistry and Biology of Pteridines and Folates. Advances in Experimental Medicine and Biology, vol 338. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2960-6_83
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DOI: https://doi.org/10.1007/978-1-4615-2960-6_83
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