当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Synthesis and evaluation of series of diazine-bridged dinuclear platinum(II) complexes through in vitro toxicity and molecular modeling: correlation between structure and activity of Pt(II) complexes.

Synthesis and evaluation of series of diazine-bridged dinuclear platinum(II) complexes through in vitro toxicity and molecular modeling: correlation between structure and activity of Pt(II) complexes.

Abstract：

:Polynuclear Pt(II) complexes are a novel class of promising anticancer agents with potential clinical significance. A series of pyrazine (pz) bridged dinuclear Pt(II) complexes with general formulas {[Pt(L)Cl]2(μ-pz)}(2+) (L, ethylenediamine, en; (±)-1,2-propylenediamine, 1,2-pn; isobutylenediamine, ibn; trans-(±)-1,2-diaminocyclohexane, dach; 1,3-propylenediamine, 1,3-pd; 2,2-dimethyl-1,3-propylenediamine, 2,2-diMe-1,3-pd) and one pyridazine (pydz) bridged {[Pt(en)Cl]2(μ-pydz)}(2+) complex were prepared. The anticancer potential of these complexes were determined through in vitro cytotoxicity assay in human fibroblasts (MRC5) and two carcinoma cell lines (A375 and HCT116), interaction with double stranded DNA through in vitro assay, and molecular docking study. All complexes inhibited cell proliferation with inhibitory concentrations in the 0.5-120 μM range. While {[Pt(1,3-pd)Cl]2(μ-pz)}(2+) showed improved activity and {[Pt(en)Cl]2(μ-pydz)}(2+) showed comparable activity to that of clinically relevant cisplatin, {[Pt(en)Cl]2(μ-pydz)}(2+) was less toxic in an assay with zebrafish (Danio rerio) embryos, causing no adverse developmental effects. The in vitro cytotoxicity of all diazine-bridged dinuclear Pt(II) complexes is discussed in correlation to their structural characteristics.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Senerovic L,Zivkovic MD,Veselinovic A,Pavic A,Djuran MI,Rajkovic S,Nikodinovic-Runic J

doi

10.1021/jm5017686

subject

Has Abstract

pub_date

2015-02-12 00:00:00

pages

1442-51

issue

3

eissn

0022-2623

issn

1520-4804

journal_volume

58

pub_type

杂志文章

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