Synthesis, characterization and preliminary cytotoxicity evaluation of five Lanthanide(III)–Plumbagin complexes

Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone, H-PLN) was isolated from Plumbago zeylanica, the anticancer traditional Chinese medicine (TCM). Five new lanthanide(III) complexes of deprotonated plumbagin: [Y(PLN)3(H2O)2] (1), [La(PLN)3(H2O)2] (2), [Sm(PLN)3(H2O)2]⋅H2O (3), [Gd(PLN)3(H2O)2] (4), and [Dy(PLN)3(H2O)2] (5) were synthesized by the reaction of plumbagin with the corresponding lanthanide salts, in amounts equal to ligand/metal molar ratio of 3:1. The PLN–lanthanide(III) complexes were characterized by different physicochemical methods: elemental analyses, UV–visible, IR and 1H NMR and ESI-MS (electrospray ionization mass spectrum) as well as TGA (thermogravimetric analysis). The plumbagin and its lanthanide(III) complexes 1–5, were tested for their in vitro cytotoxicity against BEL7404 (liver cancer) cell lines by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The five PLN–lanthanide (III) complexes 1–5 effectively inhibited BEL7404 cell lines growth with IC50 values of 11.0 ± 3.5, 5.1 ± 1.3, 6.1 ± 1.1, 6.4 ± 1.3, and 9.8 ± 1.5 μM, respectively, and exhibited a significantly enhanced cytotoxicity compared to plumbagin and the corresponding lanthanide salts, suggesting a synergistic effect upon plumbagin coordination to the Ln(III) ion. The lanthanide complexes under investigation also exerted dose- and time-dependent cytotoxic activity. [La(PLN)3(H2O)2] (2) and plumbagin interact with calf thymus DNA (ct-DNA) mainly via intercalation mode, but for [La(PLN)3(H2O)2] (2), the electrostatic interaction should not be excluded; the binding affinity of [La(PLN)3(H2O)2] (2) to DNA is stronger than that of free plumbagin, which may correlate with the enhanced cytotoxicity of the PLN–lanthanide(III) complexes.

Graphical abstractFive new lanthanide(III) complexes with plumbagin (H-PLN): [Y(PLN)3(H2O)2] (1) [La(PLN)3(H2O)2] (2), [Sm(PLN)3(H2O)2]⋅H2O (3), [Gd(PLN)3(H2O)2] (4), and [Dy(PLN)3(H2O)2] (5) were synthesized and characterized. These lanthanide complexes exhibit significantly enhanced cytotoxicity to BEL7404 vs. free plumbagin, and the interactions with DNA were studied.Figure optionsDownload full-size imageDownload as PowerPoint slide