Synthesis, structure, DNA-binding properties, and cytotoxicity of ruthenium(II) polypyridyl complexes.
Many ruthenium(II) complexes show high antitumor activities, and the in vitro antitumor activities are usually related to DNA binding. We designed and synthesized two Ru(II) polypyridyl complexes, [Ru(dmp)2(fpp)]2+ (dmp=2,9-dimethyl-1,10-phenanthroline; fpp=2-[3,4-(difluoromethylenedioxy)phenyl]imidazo[4,5-f] [1,10]phenanthroline and [Ru(phen)(2)(fpp)]2+ (phen=1,10-phenanthroline). The DNA-binding properties of these complexes have been investigated by spectroscopic titration, DNA melting experiments, viscosity measurements, and photoactivated cleavage. The mechanism studies of photocleavage revealed that singlet oxygen (1O2) and superoxide anion radical (O2(.-)) may play an important role in the photocleavage. The cytotoxicity of complexes 1 and 2 have been evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) method; complex 2 shows slightly higher anticancer potency than 1 does against all the cell lines screened.
Liu
Yun-Jun
YJ
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 51006, P. R. China. lyjche@163.com
Zeng
Cheng-Hui
CH
Yao
Jun-Hua
JH
Wu
Fu-Hai
FH
He
Li-Xin
LX
Huang
Hong-Liang
HL
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy*; D009691:Nucleic Acid Denaturation / Q000187:drug effects; D010618:Phenanthrolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D055668:Photochemical Processes / Q000187:drug effects; D017975:Ruthenium Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014783:Viscosity / Q000187:drug effects
D000970:Antineoplastic Agents; D010618:Phenanthrolines; D017975:Ruthenium Compounds; D004247:DNA; C025205:1,10-phenanthroline