Objectives Naphthalimides have shown potent antitumour activity against a variety of murine and human cancer cells. However, most of them have been abandoned because of a poor therapeutic index and haematotoxicity, such as amonafide. To overcome these disadvantages, many novel naphthalimide derivatives have been designed and synthesized as antitumour agents.
Methods The cytotoxicity of 6,6‐(propane‐1,3‐diylbis(azanediyl)bis(2‐(2‐(dimethylamino)ethyl)‐1H‐benzo[de]isoquinoline‐1‐3(2H)‐dione) (BND‐12) was evaluated using multiparameter cytotoxicity 2 kit by High Content Screening (HCS). The antiproliferative ability of BND‐12 was evaluated using MTT assay. BND‐12‐mediated cell apoptosis was evaluated using HCS. Antitumor effects and systemic toxicity of BND‐12 were evaluated in vivo using Kunming male mice.
Key findings After screening, we found BND‐12, a novel naphthalimide derivative, exerted favourable antitumour activity in vitro and in vivo. Our data demonstrated that the cytotoxicity of BND‐12 was due to cell apoptosis via the mitochondrial pathway. Interestingly, we demonstrated that BND‐12 exerted more potent antitumour activity in subcutaneous xenograft tumour growth, survival time and lung metastasis than amonafide in vivo. Encouragingly, preliminary toxicological evaluation demonstrated that BND‐12 had no obvious systemic toxicity at the therapeutic dose, especially haematotoxicity.
Conclusions BND‐12 exerted potent effects against HCC in vivo and in vitro, importantly, it had no obvious systemic toxicity at the therapeutic dose.