Novel naphthalimide derivatives as potential apoptosis-inducing agents: Design, synthesis and biological evaluation

A series of novel naphthalimide derivatives with flexible alkyl/aryl moieties were designed and synthesized. Their antitumor activities were evaluated against HeLa, A549, P388, HL-60, MCF-7, HCT-8 and A375 cancer cell lines in vitro. The preliminary results showed that most of the derivatives had comparable antitumor activities over Amonafide with the IC50 values of 10−6 to 10−5 M. More importantly, flow cytometric analysis indicated that the derivatives could effectively induce G2/M arrest and progress to apoptosis in HL-60 cell line after double staining with annexin V–FITC and propidium iodide. The present work provided a novel class of naphthalimide-based derivatives with potent apoptosis-inducing and antitumor activities for further optimization.

Graphical abstractA series of novel naphthalimide derivatives with flexible alkyl/aryl moiety were designed and synthesized. Their in vitro cytotoxic and apoptosis-inducing activities were evaluated.Figure optionsDownload full-size imageDownload as PowerPoint slide