Synthesis, characterization and biological evaluation of labile intercalative ruthenium(ii) complexes for anticancer drug screening.
DNA binding and DNA transcription inhibition is regarded as a promising strategy for cancer chemotherapy. Herein, chloro terpyridyl Ru(ii) complexes, [Ru(tpy)(N^N)Cl](+) (Ru1, N^N = 2,2'-bipyridine; Ru2, N^N = 3-(pyrazin-2-yl)-as-triazino[5,6-f]acenaphthylene; Ru3, N^N = 3-(pyrazin-2-yl)-as-triazino[5,6-f]phenanthrene; Ru4, N^N = 3-(pyrazin-2-yl)-as-triazino[5,6-f]pyrene) were prepared as DNA intercalative and covalent binding anticancer agents. The chloro ligand hydrolysis slowly and the octanol and water partition coefficient of Ru2-Ru4 were between 0.6 and 1.2. MALDI-TOF mass, DNA gel electrophoresis confirmed covalent and intercalative DNA binding modes of Ru2-Ru4, while Ru1 can only bind DNA covalently. As a result, Ru2-Ru4 exhibited stronger DNA transcription inhibition activity, higher cell uptake efficiency and better anticancer activity than Ru1. Ru4 was the most toxic complex toward all cancer cells which inhibited DNA replication and transcription. AO/EB, Annexin V/PI, nuclear staining, JC-1 assays further confirmed that Ru2-Ru4 induced cancer cell death by an apoptosis mechanism.
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, P. R. China. ceschh@mail.sysu.edu.cn.
Huaiyi
H
Huang
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, P. R. China. ceschh@mail.sysu.edu.cn.
Pingyu
P
Zhang
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, P. R. China. ceschh@mail.sysu.edu.cn.
Yu
Y
Chen
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, P. R. China. ceschh@mail.sysu.edu.cn.
Kangqiang
K
Qiu
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, P. R. China. ceschh@mail.sysu.edu.cn.
Chengzhi
C
Jin
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, P. R. China. ceschh@mail.sysu.edu.cn.
Liangnian
L
Ji
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, P. R. China. ceschh@mail.sysu.edu.cn.
Hui
H
Chao
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007364:Intercalating Agents / Q000737:chemistry / Q000494:pharmacology; D012428:Ruthenium / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D007364:Intercalating Agents; D012428:Ruthenium; D004247:DNA