Cytotoxicity of lapachol, β-lapachone and related synthetic 1,4-naphthoquinones against oesophageal cancer cells

Naphthoquinones have been found to have a wide range of biological activities, including cytotoxicity to cancer cells. The secondary metabolites lapachol, α- and β-lapachone and a series of 25 related synthetic 1,4-naphthoquinones were screened against the oesophageal cancer cell line (WHCO1). Most of the compounds exhibited enhanced cytotoxicity (IC50 1.6–11.7 μM) compared to the current drug of choice cisplatin (IC50 = 16.5 μM). This study also established that the two new synthetic halogenated compounds 12a and 16a (IC50 = 3.0 and 7.3 μM) and the previously reported compound 11a (IC50 = 3.9 μM), were non-toxic to NIH3T3 normal fibroblast cells. Cell death of oesophageal cancer cells by processes involving PARP cleavage caused by 11a was shown to be associated with elevated c-Jun levels, suggesting a role for this pathway in the mechanism of action of this cohort of naphthoquinone compounds.

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► 1,4-Naphthoquinones derivatives were obtained with antitumour activity.
► New quinonoid prototypes were developed with moderate activity against the oesophageal cancer cell line WHCO1.
► Some of the substances described were more active than lapachol and the current drug of choice cisplatin.
► Three cytotoxic compounds were found to be non-toxic against NIH3T3 normal fibroblast cells.