Sensitivity difference of rat ascites hepatoma AH-13 and mouse leukemia L-1210 to nitrosourea derivatives.

Abstract

The structure-activity relationship in different sensitivity of AH-13 and L-1210 to nitrosourea nad related derivatives was examined. N-Methyl-N-nitrosoureido derivatives, such as 1-methyl-1-nitrosourea (MNU) and 1, 1'-polymethylene-bis(3-substituted 3-nitrosourea), were inactive against AH-13 and slightly active against L-1210. On the contrary, 1, 1'-polymethylene-bis(3-substituted 1-nitrourea) derivatives were more active against AH-13 than against L-1210. The nitrosoureas which had bis(2-chloroethyl) group at the terminal were highly active against AH-13 and L-1210. One of denitrosated derivatives, 1, 1'-ethylene-bis[3-(2-chloroethyl)urea], was active against AH-13 alone. In addition, diisocyanates, nitrourea, ammonium carbamate, and 1-methyl-1-nitrourea, which are related to the nitrosourea compounds, were also tested for their activity against AH-13 and L-1210. Diisocyanates and nitrourea were active against AH-13 alone, while other compounds were all inactive.