Low toxicity cancer chemotherapy by suicide inactivation of DNA polymerase alpha holoenzyme: first results with new thiazolidinyl- and perhydrothiazinyl-ethyl-N-mustard-phosphamide esters.
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.
Hohorst
H J
HJ
Gustav-Embden-Zentrum of Biological Chemistry, University of Frankfurt/Main, Federal Republic of Germany.
Bielicki
L
L
Müller
K
K
Voelcker
G
G
D000818:Animals; D000970:Antineoplastic Agents; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors*; D007700:Kinetics; D007941:Leukemia P388 / Q000188:drug therapy* / Q000201:enzymology; D007942:Leukemia, Experimental / Q000188:drug therapy*; D051379:Mice; D009588:Nitrogen Mustard Compounds / Q000627:therapeutic use*; D013843:Thiazines / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*; D053778:Thiazolidines
D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; D013843:Thiazines; D013844:Thiazoles; D053778:Thiazolidines; C056362:NSC 612567; C056363:NSC 613060; D004257:DNA Polymerase II