Design, synthesis and biological evaluation of 3-nitro-1,8-naphthalimides as potential antitumor agents

A series of 3-nitro-naphthalimides 1(1a-1h) were designed and synthesized as antitumor agents. MTT assay results showed that all these compounds exhibited obvious antiproliferative activity against SKOV3, HepG2, A549, T-24 and SMMC-7721 Cancer cell lines, while compound 1a displayed the best antiproliferative activity against HepG2 and T-24 cell lines in comparison with mitonafide, with IC₅₀ of 9.2 ± 1.8 and 4.133 ± 0.9 μM, respectively. In vivo antiproliferative activity assay results showed that compound 1a exhibited good antiproliferative activity in the HepG2 and T-24 models, compared with mitonafide. Action mechanism results showed that compound 1a could induced the damage of DNA and the inhibition Topo I, accompanying by inducing the G2-stage arresting and the Apoptosis of T-24 Cancer cells through up-regulating expression levels of cyclin B1, CDC 2-pTy, Wee1, γH2AX, p21, Bax and cytochrome c and down-regulating expression of Bcl-2.

3-Nitro naphthalimides; Antitumor activity; Cell cycle arrest and apoptosis; DNA damage; Topo I.