Skip to main content
SpringerLink
Log in

Sulphonamide Antifolates Inhibiting Thymidylate Synthase. Synthesis, Enzyme Inhibition and Cytotoxicity

  • Chapter
Chemistry and Biology of Pteridines and Folates

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 338))

Abstract

Two quinazoline-based antifolates possessing a wide spectrum of antitumor activity, 10-propargyl-5,8-dideazafolic acid 1 and its 2-desamino-2-methyl congener 2 are strong thymidylate synthase (TS) inhibitors1. The present study concerns the effect of replacements of (i) the p-aminobenzoyl with p-aminobenzenesulphonyl moiety in parent compounds 1 and 2 and (ii) glutamyl residue with glicine, alanine, valine, riorvaline, or phenylglycine in sulphonamide analogue of 2 (compound 4). Seven new analogues 3–9 of 1 and 2 were synthesized and their activities as inhibitors of Ehrlich carcinoma thymidylate synthase and mammalian tumor cell growth tested.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. L.R. Hughes, A.L Jackman, J. Oldfield, R.C. Smith, K.D. Burrows, P.R. Marsham, J.A.M. Bishop,T.R. Jones, B.M O’Connor and A.H. Calvert, J. Med. Chem. 33:3060 (1990).

    Article  PubMed  CAS  Google Scholar 

  2. T.R. Jones, A.H. Calvert, A.L. Jackman, S.J. Brown, M Jones and K.R. Harrap, Eur. J. Cancer 17:11(1981).

    PubMed  CAS  Google Scholar 

  3. M. Jastreboff, B. Kedzierska and W. Rode, Biochem. Pharmacol 31:217 (1982).

    Article  PubMed  CAS  Google Scholar 

  4. W. Rode, T. Kulikowski, M. Jastreboff and D. Shugar, Biochem. Pharmacol. 31:2299 (1984).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Chemistry, Pedagogical University of Opole, 48 Oleska St., 45-052, Opole, Poland

    K. Pawelczak, M. Makowski & M. Kempny

  2. Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St., 02-093, Warszawa, Poland

    J. M. Dzik, M. Balińska & W. Rode

Authors
  1. K. Pawelczak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Makowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Kempny
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. M. Dzik
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Balińska
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. W. Rode
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Dept of Pharmacology College of Medicine, Universily of South Alabama, Mobile, AL, 36688, USA

    June E. Ayling

  2. Dept. of Biochemistry College of Medicine, University of South Alabama, Mobile, AL, 36688, USA

    M. Gopal Nair

  3. College of Medicine, Universily of South Alabama, Mobile, AL, 36688, USA

    Charles M. Baugh

Rights and permissions

Reprints and permissions

Copyright information

© 1993 Springer Science+Business Media New York

About this chapter

Cite this chapter

Pawelczak, K., Makowski, M., Kempny, M., Dzik, J.M., Balińska, M., Rode, W. (1993). Sulphonamide Antifolates Inhibiting Thymidylate Synthase. Synthesis, Enzyme Inhibition and Cytotoxicity. 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_129

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-2960-6_129

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6287-6

  • Online ISBN: 978-1-4615-2960-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation