Synthesis, chemical characterization, PARP inhibition, DNA binding and cellular uptake of novel ruthenium(II)-arene complexes bearing benzamide derivatives in human breast cancer cells
| Autor: | Sanja Grgurić-Šipka, Aleksandar Savić, Nevenka Gligorijević, Tamara G. Petrović, Sandra Aranđelović, Biljana Dojčinović, Siniša Radulović, Marijana Pavlović, Jelena Poljarević, Ana Tadić |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Stereochemistry
Poly ADP ribose polymerase Poly (ADP-Ribose) Polymerase-1 chemistry.chemical_element Antineoplastic Agents Breast Neoplasms Poly(ADP-ribose) Polymerase Inhibitors 010402 general chemistry Ligands 01 natural sciences Biochemistry Ruthenium Inorganic Chemistry chemistry.chemical_compound Breast cancer Coordination Complexes Cell Line Tumor Humans Benzamide Cell Proliferation chemistry.chemical_classification Antitumor agents 010405 organic chemistry BRCA1 Protein Cell Cycle Checkpoints DNA Cell cycle 0104 chemical sciences 3. Good health Enzyme PARP inhibitor chemistry Cancer cell Benzamides Mutation Drug Screening Assays Antitumor Ruthenium(II) Plasmids |
| Zdroj: | Journal of Inorganic Biochemistry |
| Popis: | Inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1) showed remarkable clinical efficacy in BRCA-mutated tumors. Based on the rational drug design, derivatives of PARP inhibitor 3-aminobenzamide (3-AB), 2-amino-4-methylbenzamide (L1) and 3-amino-N-methylbenzamide (L2), were coordinated to the ruthenium(II) ion, to form potential drugs affecting DNA and inhibiting PARP enzyme. The four conjugated complexes of formula: C1 [(ƞ6-toluene)Ru(L1)Cl]PF6, C2 [(ƞ6-p-cymene)Ru(L1)Cl]PF6, C3 [(ƞ6-toluene)Ru(L2)Cl2] and C4 [(ƞ6-p-cymene)Ru(L2)Cl2], have been synthesized and characterized. Colorimetric 3-(4.5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide (MTT) assay showed the highest antiproliferative activity of C1 in HCC1937, MDA-MB-231, and MCF-7 breast cancer cells. Efficiency of inhibition of PARP-1 enzymatic activity in vitro decreased in order: C2 > C4 > 3-AB>C1 > C3. ICP-MS study of intracellular accumulation and distribution in BRCA1-mutated HCC1937 revealed that C1-C4 entered cells within 24 h. The complex C1 showed the highest intracellular accumulation, nuclear-targeting properties, and exhibited the highest DNA binding (39.2 ± 0.6 pg of Ru per μg of DNA) that resulted in the cell cycle arrest in the S phase. This is the peer-reviewed version of the article: M. Pavlović, A. Tadić, N. Gligorijević, et al., Synthesis, chemical characterization, PARP inhibition, DNA binding and cellular uptake of novel ruthenium(II)-arene complexes bearing benzamide derivatives in human breast cancer cells, Journal of Inorganic Biochemistry, 2020, 210, 111155, doi: [https://doi.org/10.1016/j.jinorgbio.2020.111155] The published version: [https://cer.ihtm.bg.ac.rs/handle/123456789/3634] |
| Databáze: | OpenAIRE |
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