PL EN


Preferences help
enabled [disable] Abstract
Number of results
2002 | 49 | 1 | 169-176
Article title

Isophosphoramide mustard analogues as prodrugs for anti-cancer gene-directed enzyme-prodrug therapy (GDEPT).

Content
Title variants
Languages of publication
EN
Abstracts
EN
Two types of prodrugs, benzyl analogues of isophosphoramide mustard (iPAM), activated by cytochrome P450, and acylthioethyl analogues, activated by esterases, were designed. In contrast to iPAM that hydrolyse rapidly, the examined compounds are stable in phosphate-buffered saline and Tris buffer. Benzyl analogues of iPAM are poor substrates for cytochrome P450, are not cytotoxic and posses no antitumour activity. Acylthioethyl analogues of iPAM are good substrates for pig liver esterase, are cytotoxic and exert antitumour activity against L1210 leukaemia in mice. The observed correlation for iPAM analogues between their susceptibility to hydrolysis and cytotoxicity and antitumour activity suggests possible application of these compounds as the prodrugs in gene-directed enzyme-prodrug therapy.
Publisher

Year
Volume
49
Issue
1
Pages
169-176
Physical description
Dates
published
2002
received
2001-09-10
revised
2002-01-31
accepted
2002-02-14
Contributors
  • Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland
  • Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland
  • Department of Tumour Immunology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
  • Department of Tumour Immunology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
author
  • Department of Tumour Immunology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
References
  • 1. Niculescu-Duvaz, I., Spooner, R., Marais, R. & Springer, C.J. (1998) Gene-directed enzyme prodrug therapy. Bioconjugate Chem. 9, 4-22.
  • 2. Niculescu-Duvaz, I., Friedlos, F., Niculescu- -Duvaz, D., Davies, L. & Springer, C.J. (1999) Prodrugs for antibody- and gene-directed enzyme prodrug therapies (ADEPT and GDEPT). Anti-Cancer Drug Des. 14, 517-538.
  • 3. Djeha, A.H., Thomson, T.A., Leung, H., Searle, P.F., Young, L.S., Kerr, D.J., Harris, P.A., Mountain, A. & Wrighton, C.J. (2001) Combined adenovirus-mediated nitroreductase gene delivery and cb1954 treatment: A well-tolerated therapy for established solid tumors. Mol. Ther. 3, 233-240.
  • 4. Misiura, K., Okruszek, A., Pankiewicz, K., Stec, W.J., Czownicki, Z. & Utracka, B. (1983) Stereospecific synthesis of chiral metabolites of ifosfamide and their determination in the urine. J. Med. Chem. 26, 674-679.
  • 5. Spinger, J.B., Colvin, M.E., Colvin, O.M. & Ludemann, S.M. (1998) Isophosphoramide mustard and its mechanism of bisalkylation. J. Org. Chem. 63, 7218-7222.
  • 6. Engel, J., Klenner, T., Niemeyer, U., Peter, G., Schüßler, M., Schupke, H., Voss, A. & Wiessler, M. (2000) Glufosfamide. Drugs Future. 25, 791-794.
  • 7. Veyl, M., Wagner, K., Volk, C., Gorboulev, V., Baumgarten, K., Weber, W.M., Schaper, M., Bertram, B., Wiessler, M. & Koepsell, H. (1998) Transport of the new chemotherapeutic agent β-D-glucosylisophosphoramide mustard (D-19575) into tumor cells is mediated by the Na+-D-glucose cotransporter SAAT1. Proc. Natl. Acad. Sci. U.S.A. 95, 2914-2919.
  • 8. Patterson, L.H., McKeown, S.R., Robson, T., Gallagher, Raleigh, S.M. & Orr, S. (1999) Antitumour prodrug development using cytochrome P450 (CYP) mediated activation. AntiCancer Drug Des. 14, 473-486.
  • 9. Jounaidi, Y., Hecht, J.E.D. & Waxman, D.J. (1998) Retroviral transfer of human cytochrome P450 genes for oxazaphosphorine-based cancer gene therapy. Cancer Res. 58, 4391-4401.
  • 10. Valette, G., Pompon, A., Girardet, J.L., Cappellacci, L., Franchetti, P., Grifantini, La Colla, P., Loi, A.G., Perigaud, C., Gosselin, G. & Imbach, J.L. (1996) Decomposition pathways and in vitro HIV inhibitory effects of isoddA pronucleotides: Toward a rational approach for intracellular delivery of nucleoside 5'-monophosphates. J. Med. Chem. 39, 1981-1990.
  • 11. Shafiee, M., Defreme, S., Villard, A., Egron, D., Gosselin, G., Imbach, J., Lioux, T., Pompon, A., Varray, S., Aubertin, A., Mooter, G., Kinget, R., Perigaud, C. & Augustijns, P. (2001) New bis(SATE) prodrug of AZT 5'-monophosphate: In vitro anti-HIV activity, stability, and potential oral absorption. J. Pharm. Sci. 90, 448-463.
  • 12. Hładoń, B., Sloderbach, A. & Laskowska, H. (1997) Enantioselecive cytotoxic activity of bromine-substituted analogues of ifosfamide. A microsomal implication. Pol. J. Pharmacol. 49, 127-136.
  • 13. Misiura, K., Kardacka, K., Kuśnierczyk, H. (2001) Synthesis, in vitro metabolic studies, and antitumour activity of methyl analogues of ifosfamide. Arch. Pharm. Pharm. Med. Chem. 334, 291-294.
  • 14. Han, S.Y., Shulman-Roskes, E.M., Misiura, K., Anderson, L.W., Szymajda, E., Gamcsik, M.P., Chang, Y.H. & Ludeman, S.M. (1994) Synthesis of 17O (and 18O) labelled isophosphoramide mustard. J. Label. Comp. Radiopharm. 34, 247-254.
  • 15. Lefebre, I., Perigaud, C., Pompon, A., Aubertin, A.M., Girardet, J.L., Kirn, A., Gosselin, G. & Imbach, J.L. (1995) Mononucleoside phosphotriester derivatives with S-acyl-2-thioethyl bioreversible phosphate-protecting groups: Intracellular delivery of 3'-azido-2',3'-dideoxythymidine 5'-monophosphate. J. Med. Chem. 38, 3941-3950.
  • 16. Périgaud, C., Gosselin, G., & Imbach, J.L. (2000) Anti-HIV phosphotriester nucleotides. Basis for the rational design of biolabile phosphate protection; in Biomedical Chemistry/Applying Chemical Principles to the Understanding and Treatment of Disease (Torrence, P.F., ed.) pp. 115-141, John Wiley & Sons Inc., New York.
  • 17. Foster, A.B., Jarman, M., Kinas, R.W., van Maanen, J.M., Taylor, G.N., Gaston, J.L. Parkin, A. & Richardson, A.C. (1981) 5-Fluoro- and 5-chlorocyclophosphamide: Synthesis, metabolism, and antitumor activity of the cis and trans isomers. J. Med. Chem. 24, 1399-1403.
  • 18. Kwon, C.H., Moon, K.Y., Baturay, N. & Shirota, F.N. (1991) Chemically stable, lipophilic prodrugs of phosphoramide mustard as potential anticancer agents. J. Med. Chem. 34, 588-592.
Document Type
Publication order reference
Identifiers
YADDA identifier
bwmeta1.element.bwnjournal-article-abpv49i1p169kz
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.