Cytotoxicity of the traditional chinese medicine (TCM) plumbagin in its copper chemistry.
The anticancer traditional Chinese medicine (TCM), plumbagin (PLN), was isolated from Plumbago Zeylanica. Reaction of plumbagin with Cu(II) salt, afforded [Cu(PLN)(2)].2H(2)O (1). With 2,2'-bipyridine (bipy) as a co-ligand, PLN reacts with Cu(II) to give [Cu(PLN)(bipy)(H(2)O)](2)(NO(3))(2).4H(2)O (2). 1 and 2 were characterized by elemental analysis, IR, ESI-MS spectra. Their crystal structures were determined by single crystal X-ray diffraction methods. The in vitro cytotoxicity of PLN, 1 and 2 against seven human tumour cell lines was assayed. The metal-based compounds exhibit enhanced cytotoxicity vs. that of free PLN, suggesting that these compounds display synergy in the combination of metal ions with PLN. The binding properties of PLN, 1 and 2 to DNA were investigated through UV-vis, fluorescence, CD spectra, and gel mobility shift assay, which indicated that 1 and 2 were non-covalent binding and mainly intercalated the neighboring base pairs of DNA. PLN, 1 and 2 exhibit inhibition activity to topoisomerase I (TOPO I), but 1 and 2 were more effective than PLN.
Chen
Zhen-Feng
ZF
Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education), School of Chemistry & Chemical Engineering of Guangxi Normal University, Guilin, 541004, P. R. China. chenzfubc@yahoo.com
Tan
Ming-Xiong
MX
Liu
Li-Min
LM
Liu
Yan-Cheng
YC
Wang
Heng-Shan
HS
Yang
Bin
B
Peng
Yan
Y
Liu
Hua-Gang
HG
Liang
Hong
H
Orvig
Chris
C
D015082:2,2'-Dipyridyl / Q000737:chemistry; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008516:Medicine, Chinese Traditional; D008968:Molecular Conformation; D009285:Naphthoquinones / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D018517:Plant Roots / Q000737:chemistry; D029606:Plumbaginaceae / Q000737:chemistry; D059004:Topoisomerase I Inhibitors
D000972:Antineoplastic Agents, Phytogenic; D056831:Coordination Complexes; D009285:Naphthoquinones; D059004:Topoisomerase I Inhibitors; D015082:2,2'-Dipyridyl; D003300:Copper; D004247:DNA; D004264:DNA Topoisomerases, Type I; C014758:plumbagin