Synthesis of ruthenium(II) complexes and characterization of their cytotoxicity in vitro, apoptosis, DNA-binding and antioxidant activity.
A new ligand DBHIP and its two ruthenium (II) complexes [Ru(bpy)(2)(DBHIP)](ClO(4))(2) (1) and [Ru(phen)(2)(DBHIP)](ClO(4))(2) (2) have been synthesized and characterized. The binding behaviors of the two complexes to calf thymus DNA were investigated by absorption spectra, viscosity measurements, thermal denaturation and photoactivated cleavage. The DNA-binding constants for complexes 1 and 2 have been determined to be 8.87+/-0.27 x 10(4)M(-1) (s=1.83) and 1.32+/-0.31 x 10(5)M(-1) (s=1.84). The results suggest that these complexes interact with DNA through intercalative mode. The cytotoxicity of DBHIP, complexes 1 and 2 has been evaluated by MTT assay. The apoptosis assay was carried out with acridine orange/ethidium bromide (AO/EB) staining methods. The studies on the mechanism of photocleavage demonstrate that superoxide anion radical (O(2)(-)) and singlet oxygen ((1)O(2)) may play an important role.
Liu
Yun-Jun
YJ
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China. lyjche@163.com
Zeng
Cheng-Hui
CH
Liang
Zhen-Hua
ZH
Yao
Jun-Hua
JH
Huang
Hong-Liang
HL
Li
Zheng-Zheng
ZZ
Wu
Fu-Hai
FH
D000042:Absorption; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002417:Cattle; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004583:Electrons; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D017665:Hydroxyl Radical / Q000737:chemistry; D020128:Inhibitory Concentration 50; D008163:Luminescent Measurements; D009691:Nucleic Acid Denaturation; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D010618:Phenanthrolines / Q000737:chemistry; D055668:Photochemical Processes; D010957:Plasmids / Q000235:genetics; D012428:Ruthenium / Q000737:chemistry*; D044366:Transition Temperature; D014783:Viscosity
D016166:Free Radical Scavengers; D009942:Organometallic Compounds; D010618:Phenanthrolines; D017665:Hydroxyl Radical; D012428:Ruthenium; D004247:DNA