The enhancement of the activity of 10-propargyl-5,8-dideazafolate and 5,10-dideazatetrahydrofolate by inhibitors of dihydrofolate reductase Journal Article
| Authors: | Galivan, J.; Rhee, M. S.; Johnson, T. B.; Chou, T. C.; Nair, M. G.; Bunni, M.; Priest, D. |
| Article Title: | The enhancement of the activity of 10-propargyl-5,8-dideazafolate and 5,10-dideazatetrahydrofolate by inhibitors of dihydrofolate reductase |
| Abstract: | Treatment of H35 hepatoma cells with the lipid soluble dihydrofolate reductase inhibitors metoprine and trimetrexate cause a nearly 10-fold increase in the toxicity of the antipyrimidine folate analogue PDDF and the antipurine folate analogue DDATHF. Evaluation of these interactions by the combination index developed by Chou (17-20) yields results conforming to synergistic interactions. The capacity of PDDF to inhibit thymidylate synthase in intact cells as measured by tritium release from [5-3H]deoxyuridine was increased by approximately the same amount by preincubation with the dihydrofolate reductase inhibitors. The primary effect of the reductase inhibitors in causing greater activity may be a reduction in cellular folates which can cause 5,10-CH2H4PteGlun to decrease and cellular PDDF (polyglutamates) to increase. These conditions would favor inhibition of thymidylate synthase by PDDF by promoting formation of the stable, inhibited PDDF (polyglutamates)-thymidylate synthase-dUMP complex (12). © 1989. |
| Keywords: | animal; cytology; metabolism; cell survival; cell line; drug effect; tumor cells, cultured; cell culture; liver tumor; rat; drug derivative; rats; folic acid; folic acid antagonist; folic acid antagonists; hypoxanthine; quinazolines; quinazoline derivative; thymidine; liver neoplasms, experimental; tetrahydrofolates; article; support, u.s. gov't, p.h.s.; 10 propargyl 5,8 dideazafolic acid; lometrexol; hypoxanthines; tetrahydrofolic acid derivative; hypoxanthine derivative |
| Journal Title: | Advances in Enzyme Regulation |
| Volume: | 28 |
| Issue: | C |
| ISSN: | 0065-2571 |
| Publisher: | Elsevier B.V. |
| Date Published: | 1989-01-01 |
| Start Page: | 13 |
| End Page: | 16, IN9-IN10, 17-21 |
| Language: | English |
| DOI: | 10.1016/0065-2571(89)90060-5 |
| PUBMED: | 2624172 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 14 April 2020 -- Source: Scopus |
