title: Synthesis, characterization and preliminary cytotoxicity evaluation of five lanthanide(III)-plumbagin complexes.
abstract: 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.
authors.affiliation: Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), School of Chemistry & Chemical Engineering of Guangxi Normal University, Guilin, PR China. chenzfubc@yahoo.com
authors.forename: Zhen-Feng
authors.initials: ZF
authors.lastname: Chen
authors.forename: Ming-Xiong
authors.initials: MX
authors.lastname: Tan
authors.forename: Yan-Cheng
authors.initials: YC
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Peng
authors.forename: Hong-Hong
authors.initials: HH
authors.lastname: Wang
authors.forename: Hua-Gang
authors.initials: HG
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Liang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002412:Cations; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D028581:Lanthanoid Series Elements / Q000737:chemistry*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D009285:Naphthoquinones / Q000737:chemistry*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010865:Pilot Projects; D013057:Spectrum Analysis; D013818:Thermogravimetry
chemical_list: D000970:Antineoplastic Agents; D002412:Cations; D028581:Lanthanoid Series Elements; D009285:Naphthoquinones; D009942:Organometallic Compounds; D004247:DNA; C014758:plumbagin