Synthesis, chemical characterization, PARP inhibition, DNA binding and cellular uptake of novel ruthenium(II)-arene complexes bearing benzamide derivatives in human breast cancer cells
Samo za registrovane korisnike
2020
Autori
Pavlović, MarijanaTadić, Ana
Gligorijević, Nevenka
Poljarević, Jelena
Petrović, Tamara
Dojčinović, Biljana P.
Savić, Aleksandar
Radulović, Siniša
Grgurić-Šipka, Sanja
Aranđelović, Sandra
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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 cell...s 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.
Ključne reči:
Antitumor agents / Breast cancer / PARP inhibitor / Ruthenium(II)Izvor:
Journal of Inorganic Biochemistry, 2020, 210, 111155-Izdavač:
- Elsevier
Finansiranje / projekti:
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200168 (Univerzitet u Beogradu, Hemijski fakultet) (RS-200168)
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200043 (Institut za onkologiju i radiologiju Srbije, Beograd) (RS-200043)
Napomena:
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/4049
DOI: 10.1016/j.jinorgbio.2020.111155
ISSN: 0162-0134
WoS: 000564739400016
Scopus: 2-s2.0-85088982547
Kolekcije
Institucija/grupa
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Pavlović, Marijana AU - Tadić, Ana AU - Gligorijević, Nevenka AU - Poljarević, Jelena AU - Petrović, Tamara AU - Dojčinović, Biljana P. AU - Savić, Aleksandar AU - Radulović, Siniša AU - Grgurić-Šipka, Sanja AU - Aranđelović, Sandra PY - 2020 UR - https://cherry.chem.bg.ac.rs/handle/123456789/4048 AB - 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. PB - Elsevier T2 - Journal of Inorganic Biochemistry T1 - Synthesis, chemical characterization, PARP inhibition, DNA binding and cellular uptake of novel ruthenium(II)-arene complexes bearing benzamide derivatives in human breast cancer cells VL - 210 SP - 111155 DO - 10.1016/j.jinorgbio.2020.111155 ER -
@article{ author = "Pavlović, Marijana and Tadić, Ana and Gligorijević, Nevenka and Poljarević, Jelena and Petrović, Tamara and Dojčinović, Biljana P. and Savić, Aleksandar and Radulović, Siniša and Grgurić-Šipka, Sanja and Aranđelović, Sandra", year = "2020", abstract = "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.", publisher = "Elsevier", journal = "Journal of Inorganic Biochemistry", title = "Synthesis, chemical characterization, PARP inhibition, DNA binding and cellular uptake of novel ruthenium(II)-arene complexes bearing benzamide derivatives in human breast cancer cells", volume = "210", pages = "111155", doi = "10.1016/j.jinorgbio.2020.111155" }
Pavlović, M., Tadić, A., Gligorijević, N., Poljarević, J., Petrović, T., Dojčinović, B. P., Savić, A., Radulović, S., Grgurić-Šipka, S.,& Aranđelović, S.. (2020). Synthesis, chemical characterization, PARP inhibition, DNA binding and cellular uptake of novel ruthenium(II)-arene complexes bearing benzamide derivatives in human breast cancer cells. in Journal of Inorganic Biochemistry Elsevier., 210, 111155. https://doi.org/10.1016/j.jinorgbio.2020.111155
Pavlović M, Tadić A, Gligorijević N, Poljarević J, Petrović T, Dojčinović BP, Savić A, Radulović S, Grgurić-Šipka S, Aranđelović S. Synthesis, chemical characterization, PARP inhibition, DNA binding and cellular uptake of novel ruthenium(II)-arene complexes bearing benzamide derivatives in human breast cancer cells. in Journal of Inorganic Biochemistry. 2020;210:111155. doi:10.1016/j.jinorgbio.2020.111155 .
Pavlović, Marijana, Tadić, Ana, Gligorijević, Nevenka, Poljarević, Jelena, Petrović, Tamara, Dojčinović, Biljana P., Savić, Aleksandar, Radulović, Siniša, Grgurić-Šipka, Sanja, Aranđelović, Sandra, "Synthesis, chemical characterization, PARP inhibition, DNA binding and cellular uptake of novel ruthenium(II)-arene complexes bearing benzamide derivatives in human breast cancer cells" in Journal of Inorganic Biochemistry, 210 (2020):111155, https://doi.org/10.1016/j.jinorgbio.2020.111155 . .