New anticancer Pd and Pt complexes of tertamyl dithiocarbamate and DACH ligands against HT29 and Panc1 cell lines

Abstract

To investigate the reduction of side effects of commercial antitumor drugs such as cisplatin, two new platinum and palladium complexes with a formula of [M(DACH)(tertamyl.dtc)]NO3 were synthesized (DACH is 1R, 2R-diaminocyclohexane, tertamyl-dtc is tertpentyl dithiocarbamate, and M is palladium or platin ionic metals) and characterized by spectroscopic methods. The in vitro cytotoxicity of these compounds against HT29 and Panc1 cell lines showed that the IC50 values against Panc1 cell line of [Pt(DACH)(tertamyl.dtc)]NO3 and [Pd(DACH)(tertamyl.dtc)]NO3 were 263.1 and 198.7 µM, and also against HT29 cell line were 241.9 and 258.2 µM, respectively. They were similar to the value obtained for oxaliplatin and lower than cisplatin value. Thermal stability and circular dichroism results demonstrated that both metal complexes could bind to DNA via electrostatic bonds. Due to electrostatic interaction, the configuration of B-DNA to C-DNA changed, though the possibility of groove interaction may be strengthened. Furthermore, molecular docking simulation showed higher negative docking energy for [Pd(DACH)(tertamyl.dtc)]NO3 complex with a higher tendency for DNA interaction. In vitro cytotoxicity of two new Pt and Pd compounds have been studied against two cell lines (HT29 and Panc 1), which are almost equal to the value obtained for oxaliplatin and they are lower than cisplatin value. Thermal stability studies and CD results demonstrated that both complexes bind to DNA via electrostatic bonds. Further, molecular docking showed higher negative docking energy for [Pd(DACH)(tertamyl.dtc)]NO3 complex with a higher tendency for interaction. Communicated by Ramaswamy H. Sarma