Discovery of a more potent anticancer agent than C4-benzazole 1,8-naphthalimide derivatives against murine melanoma

Three novel naphthalimide-based derivatives were synthesized and tested in vitro as anticancer agents. Our previous report of the C4-benzazole 1,8-naphthalimide derivatives showed good inhibition against murine melanoma. We aimed to synthesize more potent agents and found that compound 5 reported in this article behaved 5- to 10-fold potency than our previous best results. The unique structure of compound 5 consisted of a naphthalimide framework in which C4 position was linked with an ethylenediamine group where the amino group was coupled with a 2-piconic acid moiety. Compound 5 exhibited the most potent inhibitory activity toward human DNA topoisomerase II proteins with IC₅₀ value (2.6 ± 0.1 μM) against murine B16F10 melanoma cells among the three target compounds synthesized in this study. In accordance with this finding, the results of molecular docking also revealed that compound 5 has the highest affinity with human DNA topoisomerase II among the selected compounds. Compound 5 , therefore, has high potential for becoming a lead compound.