The cytotoxicity of oleanane derived aminocarboxamides depends on their aminoalkyl substituents

Abstract

Several oligo-methylene diamine derived carboxamides of oleanolic and maslinic acid have been prepared, and substitutions of the terminal primary amine as well as variations of the length of alkyl chain of the diamine moiety were made. Biological evaluation of their cytotoxic activity was performed using photometric sulforhodamin B assays employing a panel of different human cancer cell lines. These experiments showed most of the carboxamides to be cytotoxic with EC50 values below 10\u202fµM. Prolongation of the alkyl chain length initially reduced EC50 values to a minimum, but a decrease in cytotoxicity was observed for longer alkyl chains. Variation of substituents at the terminal nitrogen atom, however, did not influence EC50 values at all. Noteworthy results were obtained particularly for compounds 4, 6 and 23 as indicated by EC50 values lower than 2\u202fµM, and in case of a maslinic derivative 23 even an increased tumor/non-tumor cell selectivity was observed. These compounds were further investigated using fluorescence microscopy and flow cytometry analysis, which revealed 6 to show indications of apoptosis.