The cytotoxicity of 22 sesquiterpenoid unsaturated dialdehydes, as determined by the neutral red absorption assay and by protein determination

The neutral red absorption assay, complemented by protein determination, was used to measure the cytotoxic activity of 22 sesquiterpenoid unsaturated dialdehydes towards hamster fibroblasts in monolayer culture (cell line V79). No significant differences between the activities determined by the two assays were found for the compounds assayed, indicating that their inhibitory effects on cell growth are related to general cytotoxicity. In spite of the apparent similarity between the chemical structures of the assayed compounds, the most active was approximately 200 times more cytotoxic than the least active. Isovelleral and its derivatives are the most cytotoxic substances, but the ranking in order of general cytotoxicity within this subgroup differed from that found in a previous study of mutagenic activity. Marasmic acid and its derivatives are also potent cytotoxic agents, but two of the most cytotoxic compounds in this group have been reported to be the least mutagenic. Such differences between cytotoxic and mutagenic activities indicate that the molecular targets for these two activities differ. The cytotoxicity of polygodial found in this study is lower than that previously reported from other cytotoxicity assays, which suggests that different tests of general cytotoxicity may have different molecular targets. Because of the diverse cytotoxic activities of the unsaturated dialdehydes, it should be possible to study them in a quantitative structure-activity relationship (QSAR) multivariate analysis.