In vitro and in vivo antitumor studies of potential anticancer agents of platinum(II) complexes of dicyclopentadiene and dithiocarbamates§.

Publication date: Aug 09, 2022

Three platinum(II) complexes of dicyclopentadiene (DCP) and dithiocarbamates (DTCs), namely, [Pt(η4-DCP)(Me2DTC)]PF6 (1), [Pt(η4-DCP)(Et2DTC)]PF6 (2), and [Pt(η4-DCP)(Bz2DTC)]PF6 (3) [Me2DTC = dimethyldithiocarbamate, Et2DTC = diethyldithiocarbamate, and Bz2DTC = dibenzyldithiocarbamate] were prepared and characterized by elemental analysis, IR, 1H, and 13C Nuclear Magnetic Resonance spectroscopy. The spectroscopic data indicated the coordination of both DCP and DTC ligands to platinum(II). The solution chemistry of complex 1 revealed that the complexes are stable in both dimethyl sulfoxide (DMSO) and 1:1 mixture of DMSO:H2O. In vitro cytotoxicity of the complexes relative to cisplatin was tested using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, against CHL-1 (human melanoma cancer cells), MDA-MB-231 (breast cancer cells), A549 (lung cancer cells), and B16 (murine melanoma cancer cells). The antiproliferative effect of all three prepared complexes was found to be significantly higher than cisplatin. Furthermore, flow cytometric analysis of complex 1 showed that the complex induced apoptosis, oxidative stress, mitochondrial potential depolarization and cell cycle arrest in a concentration-dependent pattern in the CHL-1 cells. Confirmation of apoptosis via gene expression analysis demonstrated down-regulation of anti-apoptotic genes and up-regulation of pro-apoptotic genes in the CHL-1 cells. Wound-healing assays also lent support to the strong cytotoxicity of the complexes. In vivo studies showed a significant reduction of tumor volume at the end of the experiment. In addition, the drug did not change the weight of the mice. In conclusion, complex 1 inhibited cell proliferation in vitro and reduced tumor growth in vivo.

Concepts Keywords
Arrest Chemistry
Dcpbz2dtcpf6 Physical sciences
Diethyldithiocarbamate Branches of biology
Pro Immunology
Spectroscopy Immune system
Cancer treatments
Cell signaling
Programmed cell death
Sodium diethyldithiocarbamate
T cell


Type Source Name
drug DRUGBANK Platinum
drug DRUGBANK Ditiocarb
drug DRUGBANK Dimethyl sulfoxide
drug DRUGBANK Cisplatin
disease MESH melanoma
pathway KEGG Melanoma
disease MESH cancer
disease MESH breast cancer
pathway KEGG Breast cancer
disease MESH lung cancer
pathway KEGG Apoptosis
disease MESH oxidative stress

Original Article

Leave a Comment

Your email address will not be published.