The synthesis of a series of highly functionalized DNTQ-based derivatives is described. In vitro, most of the compounds exerted a cytotoxic effect against several tumour cell lines comparable to or greater than that of doxorubicin. Here we demonstrate that compound 14, the less cardiotoxic compound of this series, induced cell differentiation and was distributed mainly in the cytoplasm in the human glioblastoma LN229 cell line. Moreover, compound 14 reduced both cellular glucose uptake and serine/threonine kinase AKT expression, and triggered cell apoptosis. These findings suggest that highly functionalized DTNQ-based derivatives are promising pharmacological tools for the study of human solid tumours.