High selectivity and significant cytotoxicity of rare earth naphthalene dicarboxylate complexes on non-small cell lung cancer cells

Abstract

Functional 1,8-naphthalimide derivatives are rapidly developing in the field of anticancer research. However, the unpredictable side effects of 1,8-naphthalimide derivatives limit their transition from clinical trials to clinical drugs. To decrease the overall cytotoxicity of 1,8-naphthalimide derivatives after coordination with metals, we have synthesized and characterized three new rare earth naphthalene dicarboxylate complexes with the general molecular formula of [Ln(TTA)₃NI-Phen], where Ln = Er, Nd, and Yb, TTA = thenoyltrifluoroacetone, and NI-Phen = 2-(1,10-phenanthrolin-5-yl)-1H-benzo[de]isoquinoline-1,3(2H)-dione. In vitro antitumor screening revealed that all three complexes exhibit better inhibitory activities against A549 and H1299 cancer cell lines compared with the commercial anticancer drug cisplatin. Especially, Er(TTA)₃NI-Phen exhibited specific cytotoxicity to H1299 cancer cells in micromole magnitude and lower toxicity to normal human cells, Beas-2b. Interestingly, Er(TTA)₃NI-Phen triggers lung cancer cell apoptosis via a mitochondrial dysfunction pathway, which is caused by dysfunction of mitochondria and cell cycle arrest. Most importantly, Er(TTA)₃NI-Phen demonstrates an inhibition rate of up to 84% against H1299 tumors.