Abstract
Two new ternary platinum(II) complexes of general formula [Pt(DTC)LCl], where DTC = 4-(2-pyridyl)piperazine-1-carbodithioate (1 and 2) and L = tri(p-tolyl)phosphine (1) and tri(o-tolyl)phosphine (2), have been synthesized and characterized. Both complexes have shown phenanthriplatin and picoplatin type axial protection, albeit from both sides, offered by CH moiety of the organophosphine (X-ray single crystal and DFT analysis). Furthermore, 2 has shown greater degree of axial shielding of platinum center than 1. In vitro anticancer activity against three cancer cell lines has revealed greater anticancer potency of 2 than 1. The activity against NF-κB (a cancer promoting protein) signified that death of the cancer cells may be due to hindering the activity of NF-κB and subsequent initiation of the apoptosis. High activity of 2 than 1 can be attributed to its greater lipophilicity and stronger axial protection (CH⋯Pt = 2.752 Å, HC⋯Pt 3.496 Å, ∠H⋯Pt-P = 78.37° and ∠ C⋯Pt-P = 64.19°), from both sides of the axial plane, that may hinder the diversion to off target biomolecules and thus may enhance cellular uptake. Based upon DNA binding and DNA denaturing studies with CT-DNA, a cooperative binding and non-intercalative (electrostatic/covalent) mode of interaction have been suggested.
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•Synthesis and characterization of Two new ternary platinum(II) dithiocarbamates•Complexes show phenanthriplatin and picoplatin type axial protection.•Complexes exhibit promising activity than cisplatin.•A cooperative binding and non-intercalative (electrostatic) mode of interaction may the reason of anticancer action.