Anticancer and DNA binding activities of platinum (IV) complexes; importance of leaving group departure rate.

Abstract:

:The two six-coordinate Pt(IV) complexes, containing bidentate nitrogen donor/methyl ligands with general formula [Pt(X)2Me2((t)bu2bpy)], where (t)bu2bpy = 4,4'-ditert-butyl-2,2'-bipyridine and X = Cl (C1) or Br (C2), serving as the leaving groups were synthesized for evaluation of their anticancer activities and DNA binding properties. To examine anticancer activities of the synthetic complexes, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and ethidium bromide/acridine orange (EB/AO) staining method were performed. The binding properties of these complexes to DNA and purine nucleotides were examined, using different spectroscopic techniques. These complexes demonstrated significant anticancer activities against three cancer cell lines Jurkat, K562, and MCF-7. On the basis of the results of EB/AO staining, C1 and C2 were also capable to induce apoptosis in cancer cells. These complexes comprise halide leaving groups, displaying different departure rates; accordingly, they demonstrated slightly dissimilar anticancer activity and significantly different DNA/purine nucleotide binding properties. The results of DNA interaction studies of these complexes suggest a mixed-binding mode, comprising partial intercalation and groove binding. Overall, the results presented herein indicate that the newly synthesized Pt(IV) complexes are promising class of the potential anticancer agents which can be considered as molecular templates in designing novel platinum anticancer drugs. This study also highlights the importance of leaving group in anticancer activity and DNA binding properties of Pt(IV) complexes.

authors

Pouryasin Z,Yousefi R,Nabavizadeh SM,Rashidi M,Hamidizadeh P,Alavianmehr MM,Moosavi-Movahedi AA

doi

10.1007/s12010-013-0700-6

subject

Has Abstract

pub_date

2014-03-01 00:00:00

pages

2604-17

issue

5

eissn

0273-2289

issn

1559-0291

journal_volume

172

pub_type

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