DNA binding properties of novel cytotoxic gold(III) complexes of terpyridine ligands: the impact of steric and electrostatic effects.
Four gold(III) complexes of terpyridine derivatives 1-4 have been synthesized and characterized by spectroscopic methods. In vitro data demonstrated that all of them showed higher cytotoxicity than cisplatin against the human non-small-cell lung cancer cell line (A-549), the human stomach carcinoma cell line (SGC-7901), the human cervix carcinoma cell line (HELA), the human colon carcinoma cell line (HCT-116), the human liver carcinoma cell line (BEL-7402), the murine leukemia cell line (P-388) and the human acute promyelocytic leukemia cell line (HL-60). Complex 3 exhibits the highest activity, with growth inhibition rates of over 80% at 10(-8) mol L(-1) against the A-549, HCT-116 and HELA tumor cell lines. Interestingly, ligands L1-L4 are also very cytotoxic against the cell lines tested. Complexes 1-4 are stable in aqueous solution for 2 days in the presence of the biological reducing agent glutathione. The inductively coupled plasma mass spectrometry data showed that DNA isolated from cells treated with complexes 1 and 3 contained gold with gold-to-nucleotide ratios of approximately 1:6,400 and 1:4,900, respectively. Fluorescence titration, UV and circular dichroism analyses proved that the steric and electrostatic effects of the ligand remarkably influence the interactions of their gold(III) complexes with DNA. The DNA binding ability of the complexes has been correlated with their cytotoxicity, which could potentially provide a new rationale for the future design of terpyridine-based metal complexes with antitumor potential.
Shi
Pengfei
P
State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, People's Republic of China.
Jiang
Qin
Q
Zhao
Yongmei
Y
Zhang
Yangmiao
Y
Lin
Jun
J
Lin
Liping
L
Ding
Jian
J
Guo
Zijian
Z
D045744:Cell Line, Tumor; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D005978:Glutathione / Q000737:chemistry; D006046:Gold / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D055672:Static Electricity
D008024:Ligands; D011725:Pyridines; D006046:Gold; D004247:DNA; D005978:Glutathione; C023666:pyridine