Comparison of the biological effects of selected 5,8-dideazafolate analogues with their 2-desamino counterparts.

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Hynes JB, Patil SA, Hagan RL, Cole A, Kohler W, Freisheim JH

Comparison of the biological effects of selected 5,8-dideazafolate analogues with their 2-desamino counterparts.

J Med Chem. 1989 Apr;32(4):852-6.

PubMed ID

2704031 [ View in PubMed

]

Abstract

Three new 5,8-dideaza analogues of folic acid devoid of an amino group at position 2 have been prepared by using synthetic routes patterned after earlier methodologies. They were 2-desamino-5,8-dideazaisofolic acid, 2b, 2-desamino-10-thia-5,8-dideazafolic acid, 2c, and 2-desamino-10-oxa-5,8-dideazafolic acid, 2d. These compounds were found to be 4-6-fold more cytoxic toward L1210 leukemia cells than their 2-NH2 counterparts and to be poor inhibitors of mammalian thymidylate synthase. However, they were only 1.5-3-fold less inhibitory toward dihydrofolate reductase than the analogous compounds containing a 2-NH2 group. The known thymidylate synthase inhibitors 2-desamino-10-propargyl-5,8-dideazafolic acid and 10-propargyl-5,8-dideazafolic acid were included in this study for purposes of comparison.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Methotrexate	Dihydrofolate reductase	IC 50 (nM)	4.3	N/A	N/A	Details