[A new inhibitor of pyrimidine phosphorylase]

N A Dmitrieva; O K Molchan; A A Komissarov; V B Sokolov; A Iu Aksinenko; A N Pushin; A N Chekhlov; V G Debabov

[A new inhibitor of pyrimidine phosphorylase]

Bioorg Khim. 1998 Dec;24(12):920-5.

[Article in Russian]

Authors

N A Dmitrieva¹, O K Molchan, A A Komissarov, V B Sokolov, A Iu Aksinenko, A N Pushin, A N Chekhlov, V G Debabov

Affiliation

¹ State Research Institute of Genetics and Selection of Industrial Microorganisms, Moscow, Russia. komissar@vnigen.msk.su

PMID: 10079951

Abstract

5,5-Bis(hydroxymethyl)-2-oxo-[1-(2-trifluoromethyl)-3,3,3- trifluoropropionamido)-1-trifluoromethyl-2,2,2-trifluoroethyl- 1,3,2-dioxaphosphan (CA-423) is an in vitro inhibitor of the Escherichia coli uridine and thymidine phosphorylases. Unlike widely studied nucleoside analogues, this compound binds to the enzymes irreversibly. Its LD50 in mice was 40 mg/kg. Due to the involvement of pyrimidine phosphorylases in carcinogenesis and the relatively low toxicity of CA-423, it is promising for anticancer therapy.

MeSH terms

Animals
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Enzyme Inhibitors / toxicity
Escherichia coli / enzymology
Lethal Dose 50
Magnetic Resonance Spectroscopy
Mice
Organophosphorus Compounds / chemistry
Organophosphorus Compounds / pharmacology*
Organophosphorus Compounds / toxicity
Propionates / chemistry
Propionates / pharmacology*
Propionates / toxicity
Thymidine Phosphorylase / antagonists & inhibitors*

Substances

CA 423
Enzyme Inhibitors
Organophosphorus Compounds
Propionates
Thymidine Phosphorylase