1st International Conference on Chemo and BioInformatics, ICCBIKG 2021, (293-296)
AUTHOR(S) / АУТОР(И): Andjela A. Franich, Ivana Vasić, Snežana Rajković, Aleksandar Arsenijević, Marija Milovanović, Nebojša Arsenijević, Jelena Milovanović, Marija D. Živković
E-ADRESS / Е-АДРЕСА: andjela.franich@pmf.kg.ac.rs
DOI: 10.46793/ICCBI21.293F
ABSTRACT / САЖЕТАК:
The series of nine dinuclear platinum(II) complexes, [{Pt(L)Cl}2(μ-X)]2+ (where L is two NH3 or 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) have been synthesized and characterized. The antitumor potential of these complexes against CT26 cells were determined by in vitro and in vivo assays. A murine model of heterotopic colon cancer tumor was induced in immunocompetent BALB/c mice for investigating antitumor potential of the Pt(II) complexes in vivo. It was found that complexes Pt1, Pt2 and Pt7 shows 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 complexes Pt5 and Pt6 exerted the highest antiproliferative effect which was evaluated by detection of Ki67 expressing cells. Complexes Pt1 and Pt2 performed significant in vivo antitumor effects reducing the growth of primary tumor and the incidence of lung and liver metastases without causing the significant hepato- and nephro- toxicity.
KEY WORDS / КЉУЧНЕ РЕЧИ:
Platinum(II) complexes; Pyridine bridging ligands; Antitumor activity; Colorectal carcinoma; CT26 cells; Apoptosis
REFERENCES / ЛИТЕРАТУРА:
N.J. Farrer, P.J. Sadler, Medicinal Inorganic Chemistry: State of the Art, New Trends, and a Vision of the Future, in: E.Alessio, Bioinorganic Medicinal Chemistry, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim (2011) 1-47.
S. Dhar, S.J. Lippard, Medicinal Inorganic Chemistry: Current Status and Mechanism of Action of Platinum- Based Anticancer Drugs, in: E.Alessio, Bioinorganic Medicinal Chemistry, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim (2011) 79-97.
L. Senerović, M.D. Živković, A. Veselinović, A. Pavić, M.I. Djuran, S. Rajković, J. Nikodinović-Runić, Synthesis and Evaluation of Series of Diazine-Bridged DinuclearPlatinum(II)Complexes through in Vitro Toxicity and Molecular Modeling: Correlation between Structure and Activity of Pt(II) Complexes, Journal of Medicinal Chemistry 58 (2015) 1442−1451.