Isohomoaminopterin and Isohomofolic Acid
Two new analogues of folic acid, isohomofolic acid and isohomoaminopterin, have been synthesized. Both compounds were prepared by reductive condensation of corresponding pteridine-6-carboxaldehydes with p -aminomethylbenzoylglutamic acid diethyl ester. Both compounds proved to be inhibitors of both...
Gespeichert in:
Veröffentlicht in: | Molecular pharmacology 1972-11, Vol.8 (6), p.740 |
---|---|
Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | Two new analogues of folic acid, isohomofolic acid and isohomoaminopterin, have been
synthesized. Both compounds were prepared by reductive condensation of corresponding
pteridine-6-carboxaldehydes with p -aminomethylbenzoylglutamic acid diethyl ester. Both
compounds proved to be inhibitors of both HeLa and Sarcoma 180 cells in tissue culture,
and also inhibited the growth of Lactobacillus casei and Streptococcus faecium . Isohomoaminopterin penetrated into Sarcoma 180 cells, whereas uptake of isohomofolic acid was not observed. The effects
of both compounds on formiminotransferase, tetrahydrofolate formylase,
dihydrofolate reductase, thymidylate synthetase, and the biosynthesis of inosinic acid were
tested. Of all these enzymes only dihydrofolate reductase was inhibited; the inhibition was
competitive with respect to folate and dihydrofolate. The inhibition by isohomoaminopterin
( K i = 12 nM with folate at pH 5.5) was two orders of magnitude greater than that by
isohomofolate. |
---|---|
ISSN: | 0026-895X 1521-0111 |