Synthesis, in vitro metabolic studies, and antitumour activity of methyl analogues of ifosfamide.
Synthesis of 2-chloro-1,1-dimethylethyl and 2-chloro-2,2-dimethylethyl analogues of ifosfamide was performed via aziridine intermediate. In vitro metabolic activation showed that both compounds are metabolised at a rate similar to the parent drug. However, their anticancer activity against L1210 leukaemia in mice was lower as compared with ifosfamide. The reduction of antitumour efficiency of examined analogues is probably caused by a lower ability to cross-link DNA by their final, active metabolites.
Misiura
K
K
Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, Poland. kmisiura@bio.cbmm.lodz.pl
Kardacka
K
K
Kusnierczyk
H
H
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis* / Q000627:therapeutic use; D007069:Ifosfamide / Q000031:analogs & derivatives*; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D013329:Structure-Activity Relationship
D018906:Antineoplastic Agents, Alkylating; D007069:Ifosfamide