Synthesis and biological activity of Na-[4-[N-[[3,4-dihydro-2-methyl-4-oxo-6-quinazolinyl]methyl]-N-propargylamino]phenylacetyl]-L-glutamic acid

• Autorzy: Kusakiewicz-Dawid A. , Bugaj M. , Dzik J.M. , Golos B. , Winska P. , Pawelczak K. , Rzeszotarska B. , Rode W.
• Języki publikacji: EN

Abstrakty

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 K value of 0.34 uM, 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 mM) 180-fold weaker than by ICI 198583 (IC50 = 6.9 uM).

Słowa kluczowe

EN

thymidine 5'-monophosphate; thymidylate synthase; inhibition; 2-deamino-2-methyl-N10-propargyl-5,8-dideazafolic acid

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2002
• Tom: 49
• Numer: 1
• Opis fizyczny: p.197-203,fig.

Twórcy

autor

Kusakiewicz-Dawid A.

• University of Opole, Opole, Poland

autor

Bugaj M.

autor

Dzik J.M.

autor

Golos B.

autor

Winska P.

autor

Pawelczak K.

autor

Rzeszotarska B.

autor

Rode W.

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