Folate analogues. 25. Synthesis and biological evaluation of N10-propargylfolic acid and its reduced derivatives.

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Ghazala M, Nair MG, Toghiyani TR, Kisliuk RL, Gaumont Y, Kalman TI

Folate analogues. 25. Synthesis and biological evaluation of N10-propargylfolic acid and its reduced derivatives.

J Med Chem. 1986 Jul;29(7):1263-9.

PubMed ID

3100797 [ View in PubMed

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Abstract

N10-Propargylfolic acid (2), which is the closest pteridine analogue of the thymidylate synthase inhibitor N10-propargyl-5,8-dideazafolic acid (PDDF), was synthesized starting from diethyl [p-(N-propargylamino)benzoyl]-L-glutamate (5) and N-(3-bromo-2-oxopropyl)phthalimide (8). The 7,8-dihydro derivative of propargylfolic acid served as a synthetic substrate of Lactobacillus casei dihydrofolate reductase. Propargylfolic acid and its reduced derivatives were weak inhibitors of L. casei thymidylate synthase compared to PDDF. All derivatives of propargylfolate were active against the growth of Streptococcus faecium, but with the exception of 7,8-dihydropropargylfolic acid, all were inactive against L. casei. Although less potent than PDDF, marked inhibition of thymidylate synthase by 2 was observed in permeabilized L1210 cells.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
10-Propargyl-5,8-Dideazafolic Acid	Thymidylate synthase	IC 50 (nM)	13	N/A	N/A	Details
Methotrexate	Thymidylate synthase	IC 50 (nM)	600000	N/A	N/A	Details