4.7 Article

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

Journal

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
Volume 38, Issue 8, Pages 2215-2228

Publisher

TAYLOR & FRANCIS INC
DOI: 10.1080/07391102.2019.1627909

Keywords

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

Funding

  1. Chemistry & Chemical Engineering Research Center of Iran

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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.

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