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Novel platinum complexes as efficient G-quadruplex DNA binders and telomerase inhibitors.

Abstract：

:Three 4-(1H-imidazo[4,5-f]-1,10-phenanthrolin-2-yl)phenol derivatives-based platinum (II) complexes have been synthesized, and their G-quadruplex DNAs-binding interactions, telomerase inhibition, antiproliferative activity, and cell cycle arrest were studied. Three complexes show the preference for stabilizing h-telo, c-kit2, and c-myc G-quadruplexes in the presence of 10-fold excess of duplex DNA and the higher binding affinities to G-quadruplexes than to duplex. The complexes 1 and 3 present a high stabilization potential (ΔTm) for h-telo G-quadruplex and thus give a significant inhibition of telomerase activity at 2μM concentration, whereas the complex 2 displays higher antiproliferative activity against HeLa and HepG2 cancer cells by MTT assay with IC50 values of about 10(-5)M. The complexes 2 and 3 arrest both cells in the G0/G1 phase of cell cycle, whereas the complex 1 arrests the cell cycle in the S phase for HeLa cells and the G0/G1 phase for HepG2 cells.

journal_name

Int J Biol Macromol

journal_title

International journal of biological macromolecules

authors

Wei C,Wen Y,Wang J

doi

10.1016/j.ijbiomac.2013.01.004

subject

Has Abstract

pub_date

2013-04-01 00:00:00

pages

185-92

eissn

0141-8130

issn

1879-0003

pii

S0141-8130(13)00011-1

journal_volume

55

pub_type

杂志文章

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