title: Preparation of 4-([2,2':6',2″-terpyridin]-4'-yl)-N,N-diethylaniline Ni(II) and Pt(II) complexes and exploration of their in vitro cytotoxic activities.
abstract: Two metal complexes of NiLCl2 (1) and [PtLCl]Cl (2) with 4-([2,2':6',2″-terpyridin]-4'-yl)-N,N-diethylaniline (L) were synthesized and characterized. 1 and 2 exhibited selective cytotoxicity to T-24 cells more than L, compared with the normal liver cell line (HL-7702). Various experiments showed that L, 1 and 2 caused T-24 cell cycle arrest at S phase, as shown by the down-regulation of cdc25 A, cyclin A, cyclin B and CDK2 and the up-regulation of p21, p27 and p53. Furthermore, complexes 1 and 2, especially complex 2, acted as telomerase inhibitors targeting c-myc G-quadruplex DNA and triggered cell apoptosis. In addition, 1 and 2 also caused mitochondrial dysfunction. Taken together, we found that 1 and 2 exerted their cytotoxic activity mainly via inhibiting telomerase by interaction with c-myc quadruplex and disruption of mitochondrial function.
authors.affiliation: State Key Laboratory Cultivation Base for The Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin 541004, PR China. Electronic address: gxnuchem@foxmail.com.
authors.forename: Hua-Hong
authors.initials: HH
authors.lastname: Zou
authors.affiliation: State Key Laboratory Cultivation Base for The Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin 541004, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Guangxi Zhuang Autonomous Region Center for Analysis and Test Research, 32 Xinghu Road, Nanning 530022, PR China.
authors.forename: Zhi-Xiang
authors.initials: ZX
authors.lastname: Long
authors.affiliation: State Key Laboratory Cultivation Base for The Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin 541004, PR China.
authors.forename: Qi-Pin
authors.initials: QP
authors.lastname: Qin
authors.affiliation: Guangxi Zhuang Autonomous Region Center for Analysis and Test Research, 32 Xinghu Road, Nanning 530022, PR China.
authors.forename: Zhong-Kui
authors.initials: ZK
authors.lastname: Song
authors.affiliation: Guangxi Zhuang Autonomous Region Center for Analysis and Test Research, 32 Xinghu Road, Nanning 530022, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xie
authors.affiliation: Guangxi Key Laboratory of Electrochemical and Magnetochemical Functional Materials, College of Chemistry and Bioengineering, Guilin University of Technology, Guilin 541004, PR China.
authors.forename: Shu-Hua
authors.initials: SH
authors.lastname: Zhang
authors.affiliation: State Key Laboratory Cultivation Base for The Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin 541004, PR China.
authors.forename: Yan-Cheng
authors.initials: YC
authors.lastname: Liu
authors.affiliation: Nanning City No. 2 People's Hospital, 13 Dancun Road, Nanning 530031, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Lin
authors.affiliation: State Key Laboratory Cultivation Base for The Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin 541004, PR China.
authors.forename: Zhen-Feng
authors.initials: ZF
authors.lastname: Chen
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D009532:Nickel / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D010984:Platinum / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D003603:Cytotoxins; D009942:Organometallic Compounds; D009944:Organoplatinum Compounds; C000611427:chloro(4-((2,2'-6',2'-terpyridin)-4'-yl)-N,N-diethylaniline)platinum(II); C000611426:dichloro(4-((2,2'-6',2'-terpyridin)-4'-yl)-N,N-diethylaniline)nickel(II); D010984:Platinum; D015082:2,2'-Dipyridyl; D009532:Nickel; D019098:Telomerase
keywords: 4-([2,2′:6′,2″-terpyridin]-4′-yl)-N,N-diethylaniline; Apoptosis; Cytotoxic activity; G-quadruplex DNA; Ni(II) and Pt(II) complexes; Telomerase