Antifolate Activity of Isoaminopterin in HeLa Cells-Reference-Cited by-同舟云学术

Antifolate Activity of Isoaminopterin in HeLa Cells

Published:1979-05 Issue:5 Volume:15 Page:730-734
ISSN:0066-4804
Container-title:Antimicrobial Agents and Chemotherapy
language:en
Short-container-title:Antimicrob Agents Chemother

Author:

Rosemond-Hornbeak Hortencia¹,Nair M. G.²

Affiliation:

1. Department of Microbiology/Immunology, University of South Alabama College of Medicine, Mobile, Alabama 36688

2. Department of Biochemistry, University of South Alabama College of Medicine, Mobile, Alabama 36688

Abstract

The antifolate activity and the transport characteristics of isoaminopterin (IA) in HeLa cells were studied and compared with those of methotrexate (MTX). Both IA and MTX inhibited the incorporation of [2- 14 C]deoxyuridine into HeLa cell DNA by 50% at a concentration of 0.09 μM by 8 h postaddition of the compounds. Unlike MTX, the inhibition of DNA synthesis by IA was time dependent and reached a maximum at 24 h. IA-induced inhibition was due to interference with folate metabolism, since it could be completely reversed with N 5 -formyl-tetrahydrofolate. Competitive transport experiments between IA and either radiolabeled MTX or radiolabeled folate showed that IA preferentially uses the reduced folate/MTX transport system. IA inhibited MTX uptake by 50% at a concentration of 6.8 μM but had a negligible effect on folate transport.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Link

https://journals.asm.org/doi/pdf/10.1128/AAC.15.5.730

Reference16 articles.

1. Folate antagonists. Annu;Bertino J. R.;Rev. Med.,1967

2. The African Iymphoma, preliminary observations on response to therapy;Burkitt D.;Cancer,1965

3. Protocols for screening chemical agents and natural products against animal tumors and other biological systems;Geran R. I.;Cancer Chemother. Rep.,1972

4. Chemical suppression of the immune response;Hitchings G. H.;Pharmacol. Rev.,1963

5. A functional, active transport system for methotrexate;Horne D. W.;Biochem. Biophy. Res. Commun.,1976

Cited by 2 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Chemistry of folic acid antagonists (a review);Pharmaceutical Chemistry Journal;1988-06

2. 6 Recent Progress in the Medicinal Chemistry of 2,4-Diaminopyrimidines;Progress in Medicinal Chemistry;1982