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)(H(2)O)(2)] (1), [La(PLN)(3)(H(2)O)(2)] (2), [Sm(PLN)(3)(H(2)O)(2)]⋅H(2)O (3), [Gd(PLN)(3)(H(2)O)(2)] (4), and [Dy(PLN)(3)(H(2)O)(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 (1)H 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 IC(50) 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)(H(2)O)(2)] (2) and plumbagin interact with calf thymus DNA (ct-DNA) mainly via intercalation mode, but for [La(PLN)(3)(H(2)O)(2)] (2), the electrostatic interaction should not be excluded; the binding affinity of [La(PLN)(3)(H(2)O)(2)] (2) to DNA is stronger than that of free plumbagin, which may correlate with the enhanced cytotoxicity of the PLN-lanthanide(III) complexes.
Copyright © 2010 Elsevier Inc. All rights reserved.