In the search for new anticancer drugs. XX: A comparison of the in vitro growth inhibition of P388 cells by TEPA and N,N;N',N'-bis (1,2-ethanediyl)-N''-(1-oxyl-2,2,6,6-tetramethyl-4- piperidinylaminocarbonyl) phosphoric triamide and congeners.
We tested the in vitro growth inhibitory activity of TEPA, and three analogs against P388 murine lymphocytic leukemia cells in culture. The analogs consist of spin-labeled TEPA and two reduced forms containing the NH and NOH groups instead of the nitroxyl function. Spin label TEPA was obtained by replacing one of the aziridine groups in TEPA with spin-labeled urea. In a concentration range of 10(-6)-10(-5) M, only the reduced analog containing the NH group was active. That is, to achieve a 50% inhibition of cell growth, a five-fold excess in concentration of this analog (IC50 = 10 X 10(-6) M) was needed as compared to the parent compound TEPA (IC50 = 2 X 10(-6) M). These results are in contrast with those obtained in vivo against the same leukemia cell line, indicating inherent discrepancies between in vivo and in vitro evaluation of antitumor agents.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001389:Azirines / Q000494:pharmacology*; D002460:Cell Line; D007941:Leukemia P388 / Q000473:pathology*; D007942:Leukemia, Experimental / Q000473:pathology*; D013329:Structure-Activity Relationship; D013852:Thiotepa / Q000494:pharmacology; D013721:Triethylenephosphoramide / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001389:Azirines; D013852:Thiotepa; C045031:N,N,N',N'-bis(1,2-ethanediyl)-N''-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinylaminocarbonyl)phosphoric triamide; D013721:Triethylenephosphoramide