Low toxicity cancer chemotherapy by suicide inactivation of DNA polymerase alpha holoenzyme: first results with new thiazolidinyl- and perhydrothiazinyl-ethyl-N-mustard-phosphamide esters

H J Hohorst; L Bielicki; K Müller; G Voelcker

doi:10.1007/BF00405840

Low toxicity cancer chemotherapy by suicide inactivation of DNA polymerase alpha holoenzyme: first results with new thiazolidinyl- and perhydrothiazinyl-ethyl-N-mustard-phosphamide esters

J Cancer Res Clin Oncol. 1988;114(3):309-11. doi: 10.1007/BF00405840.

Authors

H J Hohorst¹, L Bielicki, K Müller, G Voelcker

Affiliation

¹ Gustav-Embden-Zentrum of Biological Chemistry, University of Frankfurt/Main, Federal Republic of Germany.

PMID: 3384844
DOI: 10.1007/BF00405840

Abstract

Thiazolidinyl- and perhydrothiazinyl-ethyl-N-mustard-phosphamide esters were designed to act as highly specific suicide inactivators of DNA polymerase alpha holoenzymes. Acute and subacute toxicity of these drugs in mice was very small. By daily i.p. injection, on day 0-4 mice were cured of P 388 lymphatic leukaemia with no depression of blood leucocytes. The findings suggest that suicide inactivators of DNA polymerase alpha holoenzyme may be promising drugs for low toxicity cancer chemotherapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents*
DNA Polymerase II / antagonists & inhibitors*
Kinetics
Leukemia P388 / drug therapy*
Leukemia P388 / enzymology
Leukemia, Experimental / drug therapy*
Mice
Nitrogen Mustard Compounds / therapeutic use*
Thiazines / therapeutic use*
Thiazoles / therapeutic use*
Thiazolidines

Substances

Antineoplastic Agents
Nitrogen Mustard Compounds
Thiazines
Thiazoles
Thiazolidines
NSC 612567
NSC 613060
DNA Polymerase II