title: Synthesis of a platinum(II) complex with 2-(4-methoxy-phenyl) imidazo [4,5-f]-[1,10] phenanthrolin and study of its antitumor activity.
abstract: A new platinum(II) complex of [Pt(II)(L) (pn)]Cl·2H2O (1) (pn = 1,3-propanediamine) with 2-(4-methoxy-phenyl)imidazo [4,5-f]-[1,10]phenanthrolin (H-L) was synthesized and characterized. In complex 1, the platinum adopts a four-coordinated square planar geometry. Complex 1 exhibited selective cytotoxicity against NCI-H460, BEL-7402, SK-OV-3, SK-OV-3/DDP and HeLa cell lines with IC50 values in the micromolar range (9.7-35.8 μM), but low cytotoxicity toward normal human liver HL-7702 cells. Complex 1 caused HeLa cell cycle arrest at S phase and it induced HeLa apoptosis by the activation of caspase-3/9. Various experiments showed that complex 1 preferred to bind with G-quadruplex in c-myc. Taken together, we found that complex 1 exerted its antitumor activity mainly via inhibiting telomerase by interaction with c-myc quadruplex and activation of caspase-3/9.
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmacy of Guangxi Normal University, Yucai Road 15, Guilin 541004, PR China.
authors.forename: Qi-Pin
authors.initials: QP
authors.lastname: Qin
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmacy of Guangxi Normal University, Yucai Road 15, Guilin 541004, PR China. Electronic address: chenzfubc@yahoo.com.
authors.forename: Zhen-Feng
authors.initials: ZF
authors.lastname: Chen
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmacy of Guangxi Normal University, Yucai Road 15, Guilin 541004, PR China.
authors.forename: Wen-Ying
authors.initials: WY
authors.lastname: Shen
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmacy of Guangxi Normal University, Yucai Road 15, Guilin 541004, PR China.
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Jiang
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmacy of Guangxi Normal University, Yucai Road 15, Guilin 541004, PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Cao
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmacy of Guangxi Normal University, Yucai Road 15, Guilin 541004, PR China.
authors.forename: Yu-Lan
authors.initials: YL
authors.lastname: Li
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmacy of Guangxi Normal University, Yucai Road 15, Guilin 541004, PR China.
authors.forename: Qing-Min
authors.initials: QM
authors.lastname: Xu
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmacy of Guangxi Normal University, Yucai Road 15, Guilin 541004, PR China.
authors.forename: Yan-Cheng
authors.initials: YC
authors.lastname: Liu
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmacy of Guangxi Normal University, Yucai Road 15, Guilin 541004, PR China.
authors.forename: Ke-Bin
authors.initials: KB
authors.lastname: Huang
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmacy of Guangxi Normal University, Yucai Road 15, Guilin 541004, PR China. Electronic address: hliang@gxnu.edu.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Liang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010618:Phenanthrolines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: C000600674:2-(4-methoxy-phenyl)imidazo(4,5-f)-(1,10)phenanthroline; D000970:Antineoplastic Agents; D007093:Imidazoles; D009944:Organoplatinum Compounds; D010618:Phenanthrolines
keywords: Cell apoptosis; G-quadruplex DNA; Phenanthrolin; Platinum complex; Telomerase