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• W2104906264 abstract "Three novel cisplatin analogues were synthesized, designed according to an approach which violates the “classical” structure–activity relationship, by replacing the diamine ligands with a planar N donor heterocycle giving a sterically hindered complex. Moreover, the sterical hindrance of antitumor drug candidates potentially makes them less susceptible to deactivation by sulphur-containing proteins and helping to overcome resistance mechanisms. The resulting mononuclear complexes of sterically hindered polidentate heterocyclic N ligands [PtCl(bbp)]Cl (1) [bbp = 2,6-bis(2-benzimidazolyl)pyridine], [PtCl2(dptdn)](H2O) (2) [dptdn = sodium 5,6-diphenyl-3-(2′-pyridyl)-1,2,4-triazine-4″,4″′-disulfonate] and [(dptdn)(dpt)Pt]Cl2(H2O) (3) [dpt = 5,6-diphenyl-3-(2′-pyridyl)-1,2,4-triazine] have been prepared and structurally characterised. Both neutral and ionic complexes are present, with monofunctional (1) and bifunctional Pt(II) moieties (2) and coordinatively saturated Pt(II) ions in the mixed ligand complex (3), whose size and shape enable them to behave as novel scaffolds for DNA binding. All complexes were tested “in vitro” for their biological activity on human HT29 colorectal carcinoma and HepG2 hepatoma cells. The complexes (1) and (3), endowed with a positive charge, showed a potent cytotoxic activity and reduced cell viability with an efficacy higher than that of cisplatin; whilst the neutral bifunctional compound (2) was inactive. IC50 values have been calculated for the active compounds. The cytotoxic effects were confirmed by the accumulation of treated cells in subG0/G1 phase of cell cycle, by the loss of mitochondrial potential (Δψm) and by the chromatin condensation or fragmentation observed by means of fluorescence microscopy after Hoechst 33258 nuclear staining. A study on intracellular platinum uptake in HT29 cell line has been also performed and data obtained strongly suggest that the cytotoxicity of new tested complexes reported in this work is based on a different pharmacodynamic pattern with respect to cisplatin." @default.
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• W2104906264 date "2011-05-01" @default.
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• W2104906264 title "Synthesis, structural characterisation and biological studies of new mononuclear platinum(II) complexes with sterically hindered heterocyclic ligands" @default.
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• W2104906264 doi "https://doi.org/10.1016/j.ica.2011.01.047" @default.
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