Some new anticancer platinum complexes of dithiocarbamate derivatives against human colorectal and pancreatic cell lines

Abstract

Cisplatin, carboplatin and oxaliplatin and their analogs are effective anticancer agents, but their clinical using is limited by some serious side effects. S,S donor ligands such as dithiocarbamates can be used to reduce some side effects. In this study, some novel water soluble complexes with formula of [Pt(bpy)(R.dtc)]NO₃, where bpy is bipyridine and R.dtc is amyl-, isopentyl- or tertamyl-dtc (n-pentyl-, 3-metyl-butyl- and 2-methylbutan-dithiocarbamate, respectively) have been synthesized and characterized by elemental analysis, conductivity measurements and chemical analysis. The cytotoxic activities of synthesized complexes were investigated against human adenocarcinoma colorectal cell line (HT29) and human pancreatic cell line (Panc1), and compared with cisplatin and oxaliplatin, which display more anticancer activity for [Pt(bpy)(isopentyl.dtc)]NO₃. The experimental fluorescence and circular dichroism results illustrated partially groove binding of [Pt(bpy)(amyl.dtc)]NO₃ and [Pt(bpy)isopentyl.dtc)]NO₃ on DNA, while [Pt(bpy)(tertamyl.dtc)]NO₃ complex, can bind to DNA via intercalation. Finally, molecular docking simulation data of DNA interaction with three synthesized complexes showed [Pt(bpy)(amyl.dtc)]NO₃ complex has the highest tendency and negative docking energy in structural change of DNA.

Communicated by Ramaswamy H. Sarma

Keywords:

• Cytotoxicity
• DNA binding
• platinum complexes
• dithiocarbamate derivative
• molecular docking

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors gratefully acknowledge the financial support of this work by the Chemistry & Chemical Engineering Research Center of Iran.