Synthesis of a platinum(II) complex with 2-(4-methoxy-phenyl) imidazo [4,5-f]-[1,10] phenanthrolin and study of its antitumor activity

Qi-Pin Qin; Zhen-Feng Chen; Wen-Ying Shen; Yan-Hua Jiang; Dong Cao; Yu-Lan Li; Qing-Min Xu; Yan-Cheng Liu; Ke-Bin Huang; Hong Liang

doi:10.1016/j.ejmech.2014.10.019

Synthesis of a platinum(II) complex with 2-(4-methoxy-phenyl) imidazo [4,5-f]-[1,10] phenanthrolin and study of its antitumor activity

Eur J Med Chem. 2015 Jan 7:89:77-87. doi: 10.1016/j.ejmech.2014.10.019. Epub 2014 Oct 13.

Authors

Affiliations

¹ 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.
² 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: [email protected].
³ 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: [email protected].

PMID: 25462228
DOI: 10.1016/j.ejmech.2014.10.019

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.

Keywords: Cell apoptosis; G-quadruplex DNA; Phenanthrolin; Platinum complex; Telomerase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Cell Cycle / drug effects
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
HeLa Cells
Humans
Imidazoles / chemistry
Imidazoles / pharmacology*
Molecular Structure
Organoplatinum Compounds / chemical synthesis
Organoplatinum Compounds / chemistry
Organoplatinum Compounds / pharmacology*
Phenanthrolines / chemistry
Phenanthrolines / pharmacology*
Structure-Activity Relationship
Tumor Cells, Cultured

Substances

2-(4-methoxy-phenyl)imidazo(4,5-f)-(1,10)phenanthroline
Antineoplastic Agents
Imidazoles
Organoplatinum Compounds
Phenanthrolines