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Carrier- and receptor-mediated transport of folate antagonists targeting folate-dependent enzymes: correlates of molecular-structure and biological activity.
This folate antagonist structure-activity relationship can be of value for predicting drug sensitivity and resistance of tumor cells or drug-related toxicity to normal cells and for the rational design and development of novel antifolates. Expand
Endocytosis of GPI-linked membrane folate receptor-alpha
The data indicate that a large fraction, if not all, of internalizing MFR-alpha bypasses caveolae, and GPI-linked membrane folate receptors have been implicated in the receptor-mediated uptake of reduced folate cofactors and folate-based chemotherapeutic drugs. Expand
Hydroxylamine derivatives as potential antimalarial agents. 1. Hydroxamic acids.
  • J. Hynes
  • Chemistry, Medicine
  • Journal of medicinal chemistry
  • 1 November 1970
Improved synthesis and antitumor evaluation of 5,8-dideazaisofolic acid and closely related analogues.
The lack of antitumor activity of D-IAHQ provides indirect evidence concerning the mechanism of action of IAHQ, and the compounds having a normal folate configuration at positions 9 and 10 are more active than their reversed bridge isomers. Expand
Quinazolines as inhibitors of dihydrofolate reductase. 3. Analogs of pteroic and isopteroic acids.
A series of 19 quinazoline analogs of pteroic and isopteroic acid was prepared with particular emphasis being placed upon carboxylic acid esters, with several of the more potent inhibitors found to be inactive against L1210 leukemia in mice at low dose levels and were lethal to mice at 100 mg/kg. Expand
Synthesis and biological evaluation of a fluorescent analogue of folic acid.
The KD values for both H2PLF and PLF indicate that the fluorescein moiety does not significantly affect folate binding in enzyme binary complexes, and additional evidence suggests that an energy transfer may occur between the pteridine and the fluorespiratory moieties. Expand
Purification of mammalian tumor (L1210) thymidylate synthetase by affinity chromatography on stable biospecific adsorbent. Stabilization of the enzyme with neutral detergents.
Analytical electrophoresis of the enzyme treated with an excess of 5-fluorodeoxyuridylate and 5,10-methylenetetrahydrofolate showed the presence of two forms of thymidylates synthetase--5-fluorspecific adsorbent and 5- fluorodeoxyURidylATE, indicating that there are two binding sites for 5- fluorode Oxyuridolate present on the enzyme molecule. Expand
Quinazolines as inhibitors of dihydrofolate reductase. 4. Classical analogues of folic and isofolic acids.
A series of classical quinazoline analogues of folic and isofolic acids was evaluated for inhibitory activity against the dihydrofolate reductases from rat liver and from Streptococcus faecium, showing modest activity against L1210 leukemia in mice. Expand
Biochemical and antitumor effects of 5,8-dideazaisopteroylglutamate, a unique quinazoline inhibitor of thymidylate synthase.
The data indicate that the biochemical basis for the antitumor effects of IAHQ is probably its intracellular conversion to poly-γ-glutamyl metabolites, which inhibit thymidylate synthase via quinazoline-deoxyuridylates-enzyme ternary complex formation. Expand