title: In the search for new anticancer drugs XI. Anticancer activity of nitroxyl labeled phosphoric N,N;N',N';N",N"-tris[1,2-ethanediyl]triamide(TEPA) and phosphorothioic N,N;N',N';N",N"-tris[1,2-ethanediyl]triamide(thio-TEPA) derivatives.
abstract: In order to further evaluate the effect of the nitroxyl moiety on the anticancer activity of nitroxyl labeled analogues of phosphoric N,N;N',N';N",N"-tris[1,2-ethanediyl]triamide (TEPA) and phosphorothioic N,N;N',N';N",N"-tris[1,2-ethanediyl]triamide (thio-TEPA), the activity of these compounds was compared in vivo, using murine lymphoid leukemia L1210, with the reduced forms of the drugs, i.e. the hydroxylamines and amine congeners. At optimum dose, all compounds were active. However, the nitroxyl containing compounds were more active than the corresponding reduced forms. An admixture of 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl had no effect on the activity of thio-TEPA. Consequently, the nitroxyl moiety must be an integral part of the anticancer drug's structure in order to influence that drug's performance.
authors.forename: G
authors.initials: G
authors.lastname: Sosnovsky
authors.forename: S W
authors.initials: SW
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents; D001389:Azirines / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D007939:Leukemia L1210 / Q000188:drug therapy; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D009589:Nitrogen Oxides / Q000627:therapeutic use*; D013329:Structure-Activity Relationship; D013852:Thiotepa / Q000031:analogs & derivatives / Q000627:therapeutic use*; D013721:Triethylenephosphoramide / Q000031:analogs & derivatives / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D001389:Azirines; D009589:Nitrogen Oxides; D013852:Thiotepa; C039900:nitroxyl; D013721:Triethylenephosphoramide