Search results for "Antifolate"
showing 4 items of 4 documents
Unruptured tubal pregnancy: local low-dose therapy with methotrexate under transvaginal ultrasonographic guidance.
1996
Thirty patients with unruptured ectopic pregnancy (4-10 weeks' gestation) were treated locally with methotrexate (MTX) under sonographic guidance. The transvaginal puncture was performed under analgesic sedation using an automatic puncturing device. Local MTX therapy was successful in 25 patients (83.3%). Eighteen of these patients had received a single MTX instillation with a total dose of 10 mg, 7 patients had received a second instillation with 10 mg because of plateauing hCG levels after the first instillation. In 5 patients MTX therapy was unsuccessful. Surgical intervention was necessary within 4 h to 15 days after MTX treatment, due to severe tubal bleeding (n = 1) or the development…
Sulphonamide Antifolates Inhibiting Thymidylate Synthase. Synthesis, Enzyme Inhibition and Cytotoxicity
1993
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 n…
Quinazoline antifolate thymidylate synthase inhibitors: replacement of glutamic acid by aminophosphonic acids
2003
The synthesis of six analogues of the potent thymidylate synthase (TS) inhibitor N -[4-[ N -[(3,4-dihydro-2-methyl-4-oxo-6-quinazolinoyl)-methyl]- N -prop-2-ynylamino]benzoyl]- L -glutamic acid 2 is described in which the glutamic acid residue has been replaced by DL -aminophosphonic acids. New antifolates were tested as inhibitors of TS isolated from mouse L1210 leukemic cells as well as inhibitors of growth mouse leukemic L5178Y cells. In general these modifications result in compounds that are considerably less potent than 2 as TS inhibitors with K i 's 0.17-1.10 w M. Very poor solubility in water limited their proper assay of growth cells inhibition.
Adsorption of methotrexate and calcium leucovorin onto cholestyramine in vitro.
2003
Abstract Methotrexate (MTX), an antimetabolite of folic acid, is a drug widely used in the treatment of different types of cancer. When high doses are administered, it is necessary to interrupt its action by administering calcium leucovorin (CaL). The main pathway of MTX and CaL elimination in humans occurs through the kidney, but about 10% is excreted in the faeces via the bile. Drugs, foods and sorbents in intestinal lumen modify MTX and CaL reabsorption. Individual and simultaneous studies on the adsorption of MTX and CaL from aqueous phosphate buffer by cholestyramine were carried out in order to calculate the adsorption process of MTX and CaL to cholestyramine, and to characterize the …