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Cellular aspects of folate and antifolate membrane transport.

100%
Brzezińska A., Wińska P., Balińska M.
Acta Biochimica Polonica
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2000
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vol. 47
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issue 3
735-749
EN
Folates - one carbon carriers - take part in the metabolism of purine, thymidylate and some amino acids. Internalization of these compounds employs several mechanisms of transport systems. Reduced folate carriers and folate receptors play the most important role in this process. The physiological role of these molecules in normal and neoplastic cells is described regarding changes in transport activity and connection of transport systems with resistance to antifolates and cancer development.
2
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Synthesis and biological activity of Nα-[4-[N-[(3,4-dihydro-2-methyl-4-oxo-6-quinazolinyl)methyl]-N-propargylamino]phenyl-acetyl]-L-glutamic acid.

64%
Kusakiewicz-Dawid A., Bugaj M., Dzik J. M., Gołos B., Wińska P., Pawełczak K., Rzeszotarska B., Rode W.
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vol. 49
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issue 1
197-202
EN
2-Deamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583) is a potent inhibitor of thymidylate synthase. Its analogue, Nα-[4-[N-[(3,4-dihydro-2-methyl-4-oxo-6-quinazolinyl)methyl]-N-propargylamino]phenylacetyl]-L-glutamic acid, containing p-aminophenylacetic acid residue substituting p-aminobenzoic acid residue, was synthesized. The new analogue exhibited a moderately potent thymidylate synthase inhibition, of linear mixed type vs. the cofactor, N5,10 -methylenetetrahydrofolate. The Ki value of 0.34 μM, determined with a purified recombinant rat hepatoma enzyme, was about 30-fold higher than that reported for inhibition of thymidylate synthase from mouse leukemia L1210 cells by ICI 198583 (Hughes et al., 1990, J. Med. Chem. 33, 3060). Growth of mouse leukemia L5178Y cells was inhibited by the analogue (IC50 = 1.26 μM) 180-fold weaker than by ICI 198583 (IC50 = 6.9 μM).
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