Abstract
Molecular docked models of complex [(DEPT)Au(I)(P{Et3}] with DNA [dodecamer duplex of sequence d(CGCGAATTCGCG)2 (PDB ID: 1BNA)].
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•Gold dithiocarbamate phosphine were synthesized as antitumor chemotherapeutic agents.•All complexes exhibited strong in vitro cytotoxic effects more than the well-known cisplatin.•Molecular docking study was conducted with B–DNA to visualize the preferential docking position.•In [(CH3)3PAu(S2CN{CH3}2)] structure, gold(I) is coordinated with one P donor atom and S donor atom.
A new series of phosphanegold(I) dithiocarbamate complexes with general formula [Au(PR3)(S2CNR′2)], 1–5 (Where R=Methyl, ethyl, isopropyl and R′=Methyl, ethyl) were synthesized and characterized by elemental analysis, FTIR and multinuclear NMR spectroscopy. The molecular structure of one of them, [Au(PMe3)(S2CNMe2)] (1) was determined by single crystal X-ray crystallography, which revealed linear geometry around the Au(I) metal center. The in vitro cytotoxicity of all Au(I) complexes was studied against two human cancer cell lines, A549 and HepG2. All the complexes showed significantly higher potency (4 to 6-fold for A549 and 3 to 5-fold for HepG2 cell line) than the commercial chemotherapeutic drug, cisplatin. The in vitro DNA binding abilities of Au(I) complexes 1–5 were examined by employing different biophysical techniques, viz., UV–Vis titrations, fluorescence spectroscopy and circular dichroism. The UV–Vis titration of Au(I) complexes with CT DNA revealed that the complexes bound to CT DNA via electrostatic interactions, and the intrinsic binding constant (Kb) values for 1–5 were found to be 3.90×104, 4.74×104, 6.81×104, 8.53×104 and 2.48×104M−1 respectively, which suggested the highest binding propensity for complex 4. In addition, molecular docking studies of the Au(I) complexes were performed with B–DNA to visualize the preferential docking position, and the results showed the binding of complexes to the adenine–thymine residues in the minor groove of the DNA.