Study of the in vitro cytotoxic potential of natural and synthetic coumarin derivatives using human normal and neoplastic skin cell lines

A selection of natural and synthetic coumarin compounds, including the hydr oxylated and nitrated derivatives, were assessed for their cytotoxic potent ial using the microculture 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazo lium bromide (MTT) assay for cellular viability. For the first time this st udy utilized both human skin malignant melanocytes (SK-MEL-31) and normal h uman skin fibroblastic cells (HS613.SK), allowing identification of those c oumarin derivatives that are selectively toxic. Coumarin was found to exhib it comparatively low toxicity in both cell types, while 7-hydroxycoumarin ( 7-OHC) and coumarin had similar activity in SK-MEL-31 cells. The entire ser ies of hydroxylated coumarins were considerably more toxic in HS613.SK than in SK-MEL-31 cells, Novel synthetic nitrated coumarins, 6-nitro-7-hydroxyc oumarin (6-NO2-7-OHC) and 3,6,8-nitro-7-hydroxycoumarin (3,6,8-NO2-7-OHC), were shown to be significantly more toxic to SK-MEL-31 than HS613.SK cells. In the malignant melanocyte skin cell line (SK-MEL-31) the cytotoxic effec ts of these nitro-derivatives were shown to be dose and time dependent. The refore, the cytotoxic potential of coumarins appears to be highly dependent on the nature and position of the functional group. In addition, nitration of 7-OHC produced compounds that were cytotoxic to malignant melanocytes, suggesting that these nitro-derivatives may have a chemotherapeutic role in the future. (C) 2001 Lippincott Williams & Wilkins.