European Journal of Medicinal Chemistry 2015-01-07

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

Index: Eur. J. Med. Chem. 89 , 77-87, (2014)

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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. Copyright © 2014 Elsevier Masson SAS. All rights reserved.