Application of a multi-endpoint cytotoxicity assay to the trypanocidal compounds 2-propen-1-amine derivatives and determination of their acute toxicity

A multi-endpoint cytotoxicity method using the V79 fibroblast cell line was applied to 2-propen-1-amine derivatives and Nifurtimox that presented trypanocidal activity. The acute toxicity of the compounds was also studied using E. coli. The 2-propen-1-amine derivatives (X = p-H; p-Br; p-CH3SO2; p-NO2) exhibited higher trypanocidal activity (ID50) (trypomastigotes) 12.1-35.0 mu M) than Nifurtimox (157.0 mu M). For the cytotoxicity assessment, three independent endpoints, namely DNA content, neutral red uptake, and MTT, were used. Nifurtimox exhibited a lower toxicity (250-500 mu M) than the 2-propen-1-amine derivatives (4.9-48.0 mu M) and the 2-propen-1-amine derivatives exhibited lower EC50 values (5.7-24.0 mu M) than Nifurtimox (35.0 mu M), except for the p-CH3SO2 group whose IC50 was 110.0 mu M. Although Nifurtimox is a recognized toxic compound that needs metabolization to express its toxicity, its toxicity was lower than that of 2-propen-1-amines in all tests, Thus, we conclude that the multi-endpoint method for cytotoxicity evaluation using the V-79 fibroblast cell line is not adequate for compounds that need metabolization. This study led us to select the p-bromo 2-propen-1-amine derivative as one of the less toxic and more active trypanocide derivatives for further in vivo studies.11215316