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2002 | 49 | 2 | 407-420

Article title

Sulfamide antifolates inhibiting thymidylate synthase: synthesis, enzyme inhibition and cytotoxicity.

Content

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Languages of publication

EN

Abstracts

EN
Synthesis and biological evaluation are described of seven new analogues (3-9) of two potent thymidylate synthase inhibitors, 10-propargyl-5,8-dideazafolate (1) and its 2-methyl-2-deamino congener ICI 198583 (2). While the new compunds 3 and 4 were analogues of 1 and 2, respectively, containing a p-aminobenzenesulfonyl residue in place of the p-aminobenzoic acid residue, the remaining 5 new compounds were analogues of 4 with the L-glutamic acid residue replaced by glycine (5), L-valine (6), L-alanine (7), L-phenylglycine (8) or L-norvaline (9). The new analogues were tested as inhibitors of thymidylate synthases isolated from tumour (Ehrlich carcinoma), parasite (Hymenolepis diminuta) and normal tissue (regenerating rat liver) and found to be weaker inhibitors than the parent 10-propargyl-5,8-dideazafolic acid. Selected new analogues, tested as inhibitors of growth of mouse leukemia L 5178Y cells, were less potent than the parent 10-propargyl-5,8-dideazafolic acid. Substitution of the glutamyl residue in compound 4 with l-norvaline (9) resulted in only a 5-fold stronger thymidylate synthase inhibitor, but a 40-fold weaker cell growth inhibitor.

Year

Volume

49

Issue

2

Pages

407-420

Physical description

Dates

published
2002
received
2002-06-01
accepted
2002-06-05

Contributors

  • Institute of Chemistry, University of Opole, Opole, Poland
  • Institute of Chemistry, University of Opole, Opole, Poland
  • Institute of Chemistry, University of Opole, Opole, Poland
  • Nencki Institute of Experimental Biology, Warszawa, Poland
  • Nencki Institute of Experimental Biology, Warszawa, Poland
author
  • Nencki Institute of Experimental Biology, Warszawa, Poland
  • Institute of Chemistry, University of Opole, Opole, Poland

References

  • Bavetsias V, Jackman AL. (1998) Nonpolyglutamatable antifolates as inhibitors of thymidylate synthase (TS) and potential antitumour agents. Curr Med Chem.; 5: 265-88.
  • Calvert AH, Jones TR, Jackman AL, Brown SJ, Harrap KR. (1980) An approach to the design of antimetabolites active against cells resistant to conventional agents illustrated by quinazoline antifolates with N10-substitutions. In Human cancer, its characterisation and treatment. Davis W, Harrap KR, Stathopoulos G. eds, pp 272-83. Excerpta Medica, Amsterdam.
  • Carreras CW, Santi DV. (1995). The catalytic mechanism and structure of thymidylate synthase. Annu Rev Biochem.; 64: 721-62.
  • Dzik JM, Bretner M, Kulikowski T, Gołos B, Jarmuła A, Poznański J, Rode W, Shugar D. (1996) Synthesis and interactions with thymidylate synthase of 2,4-dithio-analogues of dUMP and 5-fluoro-dUMP. Biochim Biophys Acta.; 1293: 1-8.
  • Elslager EF, Colbry NL, Davoll J, Hutt MP, Johnson JL, Werbel LM. (1984) Folate antagonists. 22. Antimalarial and antibacterial effects of 2,4-diamino-6-quinazolinesulfonamides. J Med Chem.; 27: 1740-3.
  • Georgopapadakou NH, Walsh TJ. (1996) Antifungal agents: chemotherapeutic targets and immunologic strategies. Antimicrob Agents Chemother.; 40: 279-91.
  • Greenstein JP, Winitz M. (1961) In Chemistry of Amino Acids. Vol. 2, p 934. Wiley, New York.
  • Harrap KR. (1995) Initiatives with platinum- and quinazoline-based antitumor molecules. Fourteenth Bruce F. Cain memorial award lecture. Cancer Res.; 55: 2761-8.
  • Heidelberger C, Danenberg PV, Moran RG. (1983) Fluorinated pyrimidines and their nucleosides. Adv Enzymol.; 54: 58-119.
  • Hughes LR, Jackman AL, Oldfield J, Smith RC, Burrows KD, Marsham PR, Bishop JAM, Jones TR, O'Connor BM, Calvert AH. (1990) Quinazoline antifolate thymidylate synthase inhibitors: alkyl, substituted alkyl, and aryl substituents in the C2 position. J Med Chem.; 33: 3060-7.
  • Jackman AL, Farrugia DC, Gibson W, Kimbell R, Harrap KR, Stephens TC, Azab M, Boyle FT. (1995) ZD1694 (Tomudex): a new thymidylate synthase inhibitor with activity in colorectal cancer. Eur J Cancer.; 31A: 1277-82.
  • Jackman AL, Newell DR, Gibson W, Jordel DI, Taylor GA, Bishop JAM, Hughes LR, Calvert AH. (1991) The biochemical pharmacology of the thymidylate synthase inhibitor, 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 188583). Biochem Pharmacol.; 42: 1885-95.
  • Jastreboff M, Kędzierska B, Rode W. (1983) Properties of thymidylate synthase from Ehrlich ascites carcinoma cells. Biochem Pharmacol.; 31: 217-23.
  • Jones TR, Smithers MJ, Betteridge RF, Taylor AM, Jackman AL, Calvert AH, Davies LC, Harrap KR. (1986) Quinazoline antifolates inhibiting thymidylate synthase: variation of the amino acid. J Med Chem.; 29: 1114-8.
  • Jones TR, Thornton TJ, Flinn A, Jackman AL, Newell DR, Calvert AH. (1989) Quinazoline antifolates inhibiting thymidylate synthase: 2-desamino derivatives with enhanced solubility and potency. J Med Chem.; 32: 847-52.
  • Jones TR, Varney MD, Webber SE, Lewis KK, Marzoni GP, Palmer CL, Kathardekar V, Welsh KM, Webber S, Matthews DA, Appelt K, Smith WW, Janson CA, Villafranca JE, Bacquet RJ, Howland EF, Bartlett CA, Morse CA. (1996) Structure-based design of lipophilic quinazoline inhibitors of thymidylate synthase. J Med Chem.; 39: 904-17.
  • Kusakiewicz-Dawid A, Bugaj M, Dzik JM, Gołos B, Wińska P, Pawełczak K, Rzeszotarska B, Rode W. (2002) Synthesis and biological activity of Na-[4-[N-[(3,4-dihydro-2-methyl-4-oxo- 6-quinazolinyl)methyl]-N-propargylamino]phe-nylacetyl]-L-glutamic acid. Acta Biochim Polon.; 49: 197-203.
  • Marsham PR, Jackman AL, Barker AJ, Boyle FT, Pegg SJ, Wardleworth JM, Kimbell R, O'Connor BM, Calvert AH, Hughes LR. (1995) Quinazoline antifolate thymidylate synthase inhibitors: replacement of glutamic acid in the C2-methyl series. J Med Chem.; 38: 994-1004.
  • Marsham PR, Jackman AL, Oldfield J, Hughes LR, Thornton TJ, Bisset GMF, O'Connor BM, Bishop JAM, Calvert AH. (1990) Quinazoline antifolate thymidylate synthase inhibitors: benzoyl ring modifications in the C2-methyl series. J Med Chem.; 33: 3072-8.
  • Pendergast W, Dickerson SH, Johnson JV, Dev IK, Ferone R, Duch DS, Smith GK. (1993) Benzoquinazoline inhibitors of thymidylate synthase: enzyme inhibitory activity and cytotoxicity of some sulfonamidobenzoylglutamate and related derivatives. J Med Chem.; 36: 3464-71.
  • Rathod PK. (1997) Antimalarial agents directed at thymidylate synthase. J Pharm Pharmacol.; 49 (Suppl. 2): 704-11.
  • Rode W, Kulikowski T, Kędzierska B, Jastreboff M, Shugar D. (1984) Inhibition of mammalian tumour thymidylate synthetase by 5-alkylated 2'-deoxyuridine 5'-phosphates. Biochem Pharmacol.; 33: 2699-705.
  • Rode W, Zieliński Z, Dzik JM, Kulikowski T, Bretner M, Kierdaszuk B, Cieśla J, Shugar D. (1990) Mechanism of inhibition of mammalian tumor and other thymidylate synthases by N4-hydroxy-dCMP, N4-hydroxy-5-fluoro-dCMP, and related analogues. Biochemistry.; 29: 10835-42.
  • Roeske R. (1963) Preparation of t-butyl esters of free amino acids. J Org Chem.; 28: 1251-3.
  • Rosowsky A. (1992) Development of new antifolate analogs as anticancer agents. Am J Pharmceut Education.; 56: 453-63.
  • Synold TW, Willits EM, Barredo JC. (1996) Role of folylpolyglutamate synthetase (FPGS) in antifolate chemotherapy; a biochemical and clinical update. Leukemia Lymphoma.; 21: 9-15.
  • Takemura Y, Jackman AL. (1997) Folate-based thymidylate synthase inhibitors in cancer chemotherapy. Anti-Cancer Drugs.; 8: 3-16.
  • Varney MD, Marzoni GP, Palmer CL, Deal JG, Webber S, Welsh KM, Bacquet RJ, Barlett CA, Morse CA, Booth CLJ, Herrmann SM, Howland EF, Ward RW, White J. (1992) Crystal structure-based design and synthesis of benzo[cd]indole-containing inhibitors of thymidylate synthase. J Med Chem.; 35: 663-76.

Document Type

Publication order reference

Identifiers

YADDA identifier

bwmeta1.element.bwnjournal-article-abpv49i2p407kz
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