Synthesis and characterization of Pt(II) based potent anticancer agents with minimum normal cell toxicity: their bio-activity and DNA binding property
Pt(II) based complex [Pt(DMEEDA)Cl2]; 1 (where DMEEDA = N,N-Dimethyl-N'-ethylethylenediamine) was synthesised where DMEEDA acts as (N,N) bidentate carrier ligands. Diaqua complex [Pt(DMEEDA)(H2O)2](NO3)2; 2, was obtained by hydrolysis of dichloro complex 1. Further, its substituted complex [Pt(DMEEDA)(L-cys)](NO3); 3 and [Pt(DMEEDA)(N-ac-L-cys)]; 4 (where, L-cys = L-cysteine and N-ac-L-cys = N-acetyl-L-cysteine) were synthesised with amino acid L-cysteine and its acetyl derivative. The complexes were characterized with different spectroscopic techniques like UV-Vis, FT-IR, 1H NMR and ESI-MS. The structure of complex 1 has been determined by X-ray diffraction study and crystal system (orthorhombic) with its cell parameters a = 7.9970(2) Å, b= 16.9851(7) Å, c =16.0460(7) Å and α = 90(o); β = 90(o); γ = 90(o) and space group (pccn) were found. DNA binding property of the complexes was investigated with Gel electrophoresis experiment and DNA binding constants were obtained from UV-Vis spectroscopic and fluorescence titration methods. Congruent with significant increase in DNA fragmentation, growth inhibition potential of synthesized Pt(II) complexes has been remarkably higher on hepatocarcinoma cell line (HepG2), compared to cisplatin. Moreover, these complexes show minimal toxicity to mouse primary hepatocytes and RAW 264.7 cells in vitro.