In vitro and in vivoactivity of series of cationic dinuclearPt(II) complexes

• Published in: Journal of inorganic biochemistry 2021-12, Vol.225, p.111619, Article 111619
• Main Authors: Vasić, Ivana, Rajković, Snežana, Arsenijević, Aleksandar, Milovanović, Marija, Arsenijević, Nebojša, Milovanović, Jelena, Živković, Marija D.
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Antitumour activity; Apoptosis; Apoptosis - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Colorectal carcinoma; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Coordination Complexes - therapeutic use; CT26 cells; Drug Screening Assays, Antitumor; G2 Phase Cell Cycle Checkpoints - drug effects; Ligands; Male; Mice; Mice, Inbred BALB C; Molecular Structure; Neoplasm Metastasis - prevention & control; Neoplasms - drug therapy; Platinum - chemistry; Platinum(II) complexes; Pyridine bridging ligands
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2021.111619

The antitumour potential of nine dinuclear platinum(II) complexes of the type [{Pt(L)Cl}2(μ-X)]2+(where L represents two NH3 or different bidentantly coordinated diamine ligand - ethylenediamine, en; (±)-1,2-propylenediamine, 1,2-pn; isobutylenediamine, ibn; trans-(±)-1,2-diaminocyclohexane, dach; 1,3-propylenediamine, 1,3-pd; 2,2-dimethyl-1,3-propylenediamine, 2,2-diMe-1,3-pd; (±)-1,3-pentanediamine,1,3-pnd, and X is a bridging pyrazine (pz) or pyridazine (pydz) ligand) were determined by in vitro and in vivo assays using the CT26 cell line and a murine model of heterotopic colon cancer tumour induced in immunocompetent BALB/c mice. This study concludes that complexes Pt1, Pt2 and Pt7 possess significant in vitro cytotoxic activity against mouse colon carcinoma CT26 cells, while all these complexes show moderate apoptotic effect. Complexes Pt1 and Pt7 arrested CT26 cells in G2/M phase of cell cycle, while, evaluated by detection of Ki67 expressing cells, complexes Pt5 and Pt6 exerted the highest antiproliferative effect. Complexes Pt1 and Pt2 exerted significant in vivo antitumour effects. These complexes reduced the growth of primary tumour and the incidence of lung and liver metastases without causing the significant hepato- and nephro- toxicity. Our data indicate considerable antitumour activity of platinum(II) complexes against CT26 cells in vitro and in vivo and imply possible further investigations on their role as potential chemotherapeutic agents. From nine cationic dinuclear Pt(II) complexes (Pt1-Pt9) the highest in vitro cytotoxic activity against CT26 cells showed Pt1. Furthermore, Pt1 showed significant in vivo antitumor effect. It reduced the growth of primary murine colon cancer and reduced the incidence of lung and liver metastases, without significant liver- and nephro-toxicity. [Display omitted] •Complexes Pt1, Pt2, Pt7 possess significant in vitro cytotoxicity against CT26 cells.•Pt1 and Pt7 arrested CT26 cells in G2/M phase of cell cycle.•Complexes Pt1 and Pt2 exerted significant in vivo antitumor effects.•Pt1 and Pt2 reduce the growth of primary tumour and lung and liver metastases.•Liver- and nephro- toxicity was not induced significantly.