Synthesis and Evaluation of Series of Diazine-Bridged Dinuclear Platinum(II) Complexes through in Vitro Toxicity and Molecular Modeling: Correlation between Structure and Activity of Pt(II) Complexes
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2015
Authors
Šenerović, LidijaŽivković, Marija D.
Veselinović, Aleksandar
Pavić, Aleksandar
Djuran, Milos I.
Rajković, Snežana
Nikodinović-Runić, Jasmina
Article (Published version)
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Polynuclear Pt(II) complexes are a novel class of promising anticancer agents with potential clinical significance. A series of pyrazine (pz) bridged dinuclear Pt(II) complexes with general formulas {[Pt(L)Cl](2)(mu-pz)}(2+) (L, 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) and one pyridazine (pydz) bridged {[Pt(en)Cl](2)(mu-pydz)}(2+) complex were prepared. The anticancer potential of these complexes were determined through in vitro cytotoxicity assay in human fibroblasts (MRC5) and two carcinoma cell lines (A375 and HCT116), interaction with double stranded DNA through in vitro assay, and molecular docking study. All complexes inhibited cell proliferation with inhibitory concentrations in the 0.5-120 mu M range. While {[Pt(1,3-pd)Cl](2)(mu-pz)}(2+) showed improved activity and {[Pt(en)Cl](2)(mu-pydz)}(2+) showed comparable act...ivity to that of clinically relevant cisplatin, {[Pt(en)Cl](2)(mu-pydz)}(2+) was less toxic in an assay with zebrafish (Danio rerio) embryos, causing no adverse developmental effects. The in vitro cytotoxicity of all diazine-bridged dinuclear Pt(II) complexes is discussed in correlation to their structural characteristics.
Source:
Journal of Medicinal Chemistry, 2015, 58, 3, 1442-1451Publisher:
- Amer Chemical Soc, Washington
Funding / projects:
- Synthesis of new metal complexes and investigation of their reactions with peptides (RS-MESTD-Basic Research (BR or ON)-172036)
- Microbial diversity study and characterization of beneficial environmental microorganisms (RS-MESTD-Basic Research (BR or ON)-173048)
DOI: 10.1021/jm5017686
ISSN: 0022-2623
PubMed: 25551180
WoS: 000349573800033
Scopus: 2-s2.0-84922826336
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Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Šenerović, Lidija AU - Živković, Marija D. AU - Veselinović, Aleksandar AU - Pavić, Aleksandar AU - Djuran, Milos I. AU - Rajković, Snežana AU - Nikodinović-Runić, Jasmina PY - 2015 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/861 AB - Polynuclear Pt(II) complexes are a novel class of promising anticancer agents with potential clinical significance. A series of pyrazine (pz) bridged dinuclear Pt(II) complexes with general formulas {[Pt(L)Cl](2)(mu-pz)}(2+) (L, 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) and one pyridazine (pydz) bridged {[Pt(en)Cl](2)(mu-pydz)}(2+) complex were prepared. The anticancer potential of these complexes were determined through in vitro cytotoxicity assay in human fibroblasts (MRC5) and two carcinoma cell lines (A375 and HCT116), interaction with double stranded DNA through in vitro assay, and molecular docking study. All complexes inhibited cell proliferation with inhibitory concentrations in the 0.5-120 mu M range. While {[Pt(1,3-pd)Cl](2)(mu-pz)}(2+) showed improved activity and {[Pt(en)Cl](2)(mu-pydz)}(2+) showed comparable activity to that of clinically relevant cisplatin, {[Pt(en)Cl](2)(mu-pydz)}(2+) was less toxic in an assay with zebrafish (Danio rerio) embryos, causing no adverse developmental effects. The in vitro cytotoxicity of all diazine-bridged dinuclear Pt(II) complexes is discussed in correlation to their structural characteristics. PB - Amer Chemical Soc, Washington T2 - Journal of Medicinal Chemistry T1 - Synthesis and Evaluation of Series of Diazine-Bridged Dinuclear Platinum(II) Complexes through in Vitro Toxicity and Molecular Modeling: Correlation between Structure and Activity of Pt(II) Complexes EP - 1451 IS - 3 SP - 1442 VL - 58 DO - 10.1021/jm5017686 ER -
@article{ author = "Šenerović, Lidija and Živković, Marija D. and Veselinović, Aleksandar and Pavić, Aleksandar and Djuran, Milos I. and Rajković, Snežana and Nikodinović-Runić, Jasmina", year = "2015", abstract = "Polynuclear Pt(II) complexes are a novel class of promising anticancer agents with potential clinical significance. A series of pyrazine (pz) bridged dinuclear Pt(II) complexes with general formulas {[Pt(L)Cl](2)(mu-pz)}(2+) (L, 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) and one pyridazine (pydz) bridged {[Pt(en)Cl](2)(mu-pydz)}(2+) complex were prepared. The anticancer potential of these complexes were determined through in vitro cytotoxicity assay in human fibroblasts (MRC5) and two carcinoma cell lines (A375 and HCT116), interaction with double stranded DNA through in vitro assay, and molecular docking study. All complexes inhibited cell proliferation with inhibitory concentrations in the 0.5-120 mu M range. While {[Pt(1,3-pd)Cl](2)(mu-pz)}(2+) showed improved activity and {[Pt(en)Cl](2)(mu-pydz)}(2+) showed comparable activity to that of clinically relevant cisplatin, {[Pt(en)Cl](2)(mu-pydz)}(2+) was less toxic in an assay with zebrafish (Danio rerio) embryos, causing no adverse developmental effects. The in vitro cytotoxicity of all diazine-bridged dinuclear Pt(II) complexes is discussed in correlation to their structural characteristics.", publisher = "Amer Chemical Soc, Washington", journal = "Journal of Medicinal Chemistry", title = "Synthesis and Evaluation of Series of Diazine-Bridged Dinuclear Platinum(II) Complexes through in Vitro Toxicity and Molecular Modeling: Correlation between Structure and Activity of Pt(II) Complexes", pages = "1451-1442", number = "3", volume = "58", doi = "10.1021/jm5017686" }
Šenerović, L., Živković, M. D., Veselinović, A., Pavić, A., Djuran, M. I., Rajković, S.,& Nikodinović-Runić, J.. (2015). Synthesis and Evaluation of Series of Diazine-Bridged Dinuclear Platinum(II) Complexes through in Vitro Toxicity and Molecular Modeling: Correlation between Structure and Activity of Pt(II) Complexes. in Journal of Medicinal Chemistry Amer Chemical Soc, Washington., 58(3), 1442-1451. https://doi.org/10.1021/jm5017686
Šenerović L, Živković MD, Veselinović A, Pavić A, Djuran MI, Rajković S, Nikodinović-Runić J. Synthesis and Evaluation of Series of Diazine-Bridged Dinuclear Platinum(II) Complexes through in Vitro Toxicity and Molecular Modeling: Correlation between Structure and Activity of Pt(II) Complexes. in Journal of Medicinal Chemistry. 2015;58(3):1442-1451. doi:10.1021/jm5017686 .
Šenerović, Lidija, Živković, Marija D., Veselinović, Aleksandar, Pavić, Aleksandar, Djuran, Milos I., Rajković, Snežana, Nikodinović-Runić, Jasmina, "Synthesis and Evaluation of Series of Diazine-Bridged Dinuclear Platinum(II) Complexes through in Vitro Toxicity and Molecular Modeling: Correlation between Structure and Activity of Pt(II) Complexes" in Journal of Medicinal Chemistry, 58, no. 3 (2015):1442-1451, https://doi.org/10.1021/jm5017686 . .