title: Ruthenium(II) complexes as apoptosis inducers by stabilizing c-myc G-quadruplex DNA.
abstract: Two ruthenium(II) complexes, [Ru(L)2(p-tFMPIP)](ClO4)2 (L = bpy, 1; phen, 2; p-tFMPIP = 2-(4-(trifluoromethyphenyl)-1H-imidazo[4,5f][1,10] phenanthroline)), were prepared by microwave-assisted synthesis technology. The inhibitory activity evaluated by MTT assay shown that 2 can inhibit the growth of MDA-MB-231 cells with inhibitory activity (IC50) of 16.3 μM, which was related to the induction of apoptosis. Besides, 2 exhibit low toxicity against normal HAcat cells. The inhibitory growth activity of both complexes related to the induction of apoptosis was also confirmed. Furthermore, the studies on the interaction of both complexes with c-myc G4 DNA shown that 1 and 2 can stabilize the conformation of c-myc G4 DNA in groove binding mode, which has been rational explained by using DFT theoretical calculation methods. In a word, this type of ruthenium(II) complexes can act as potential apoptosis inducers with low toxicity in clinic by stabilizing c-myc G4 DNA.
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, PR China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, PR China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, PR China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Wu
authors.affiliation: Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, PR China. Electronic address: sunfenyong@263.net.
authors.forename: Fen-Yong
authors.initials: FY
authors.lastname: Sun
authors.affiliation: School of Pharmacy, Guangdong Medical College, Zhanjiang 524023, PR China.
authors.forename: Lan-Mei
authors.initials: LM
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Guangdong Medical College, Zhanjiang 524023, PR China.
authors.forename: Jin-Chan
authors.initials: JC
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, PR China.
authors.forename: Shu-Ling
authors.initials: SL
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, PR China. Electronic address: wenjiemei@126.com.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Mei
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D054856:G-Quadruplexes / Q000187:drug effects*; D006801:Humans; D010618:Phenanthrolines / Q000737:chemistry; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D012428:Ruthenium / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D010618:Phenanthrolines; D016271:Proto-Oncogene Proteins c-myc; D012428:Ruthenium; D004247:DNA
keywords: Apoptosis induction; Microwave-assisted synthesis; Ruthenium(II) complexes; c-myc G4 DNA