2-(3,5-Dibromo-4-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthrolinoruthenium(II) complexes: synthesis, characterization, cytotoxicity, apoptosis, DNA-binding and antioxidant activity.
A new ligand DBHIP and its two ruthenium(II) complexes [Ru(dmb)(2)(DBHIP)](ClO(4))(2) (1) and [Ru(dmp)(2)(DBHIP)](ClO(4))(2) (2) have been synthesized and characterized. The cytotoxicity of DBHIP and complexes 1 and 2 has been assessed by MTT assay. The apoptosis studies were carried out with acridine orange/ethidium bromide (AO/EB) staining methods. The binding behaviors of these complexes to calf thymus DNA (CT-DNA) were studied by absorption titration, viscosity measurements, thermal denaturation and photoactivated cleavage. The DNA-binding constants of complexes 1 and 2 were determined to be 8.64 +/- 0.16 x 10(4) (s = 1.34) and 2.79 +/- 0.21 x 10(4) (s = 2.17) M(-1). The results suggest that these complexes interact with DNA through intercalative mode. 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 in the DNA cleavage. The experiments on antioxidant activity show that these compounds also exhibit good antioxidant activity against hydroxyl radical (OH*).
Liu
Yun-Jun
YJ
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, People's Republic of China. lyjche@163.com
Liang
Zhen-Hua
ZH
Li
Zheng-Zheng
ZZ
Zeng
Cheng-Hui
CH
Yao
Jun-Hua
JH
Huang
Hong-Liang
HL
Wu
Fu-Hai
FH
D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002417:Cattle; D002460:Cell Line; D004247:DNA / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D053837:DNA Cleavage / Q000187:drug effects; D008024:Ligands; D015394:Molecular Structure; D009691:Nucleic Acid Denaturation; D010618:Phenanthrolines / Q000737:chemistry*; D017975:Ruthenium Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014783:Viscosity
D000975:Antioxidants; D008024:Ligands; D010618:Phenanthrolines; D017975:Ruthenium Compounds; D004247:DNA; C427203:calf thymus DNA