Synthesis and testing of quinone-based bis(2,2-dimethyl-1-aziridinyl)phosphinyl carbamates as radiation-potentiating antitumor agents.
Two new drug candidates, in which a quinonoid moiety is linked to the reactive bis(2,2-dimethyl-1-aziridinyl)phosphinyl function, have been prepared and tested in vivo for antitumor activity and in vitro as potentiators of the cytotoxic effect of X-irradiation. Without irradiation only moderate effectiveness against leukemia P-388 in mice was exhibited by one of the quinonoid compounds that had sufficient water solubility to be used in the in vivo screening. However, both compounds were shown to potentiate the effect of X-irradiation in vitro by a colony-forming cell culture assay under hypoxic conditions.
Zhang
S F
SF
Department of Medicinal Chemistry, State University of New York, Buffalo 14260.
Earle
J
J
MacDiarmid
J
J
Bardos
T J
TJ
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D008811:Mice, Inbred DBA; D011809:Quinones / Q000138:chemical synthesis* / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D011809:Quinones; D011838:Radiation-Sensitizing Agents