RESUMO
A number of recently synthesized mono- and bis(1-aziridinyl) derivatives of the inorganic ring systems (NPCl2)3 and (NPCl2)4 was tested for their cytostatic activity in vitro (L1210 and L5178Y cells) and in vivo (intraperitoneal leukemia L1210 in CDF1 mice). Generally, the nongeminal bis(1-aziridinyl) isomers (either trans or cis) appear to be potent tumor growth inhibitors in contrast to their geminally substituted and mono(1-aziridinyl)-substituted analogues. A relationship between the biological activity and the number of alkylating centers (i.e., P atoms carrying one or two aziridinyl groups) is proposed.
Assuntos
Antineoplásicos/uso terapêutico , Aziridinas/uso terapêutico , Azirinas/uso terapêutico , Compostos Organofosforados/uso terapêutico , Animais , Sobrevivência Celular/efeitos dos fármacos , Isomerismo , Leucemia L1210/tratamento farmacológico , Leucemia L5178/tratamento farmacológico , Masculino , Camundongos , Relação Estrutura-AtividadeRESUMO
Six representatives of inorganic cyclic systems (NPAz2)2 NSOX(Az = aziridino, X = F, Az, Ph) and (NPAz2)2 NPAzR [R = Az, Morph (morpholino), Pyr (pyrrolidino)] show cytostatic activity in an in vitro screening system. The technique of the in vitro screening system used is described. L5178Y and Ehrlich ascites cells are grown as suspension cultures in concave-bottomed wells in microtiter test plates using serial dilutions of the drugs in the medium. The diameter of the cell sedimentation spots, which can be compared visually is taken to determine the lowest active dose. The results of this test correspond with the cytostatic activities observed in former in vivo experiments.
