Synthesis, chemical characterization, PARP inhibition, DNA binding and cellular uptake of novel ruthenium(II)-arene complexes bearing benzamide derivatives in human breast cancer cells
Autori
Pavlović, MarijanaTadić, Ana
Gligorijević, Nevenka
Poljarević, Jelena
Petrović, Tamara G.
Dojčinović, Biljana
Savić, Aleksandar
Radulović, Siniša
Članak u časopisu (Recenzirana 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-MESTD-inst-2020-200168)
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200043 (Institut za onkologiju i radiologiju Srbije, Beograd) (RS-MESTD-inst-2020-200043)
Napomena:
- 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
DOI: 10.1016/j.jinorgbio.2020.111155
ISSN: 0162-0134
PubMed: 32768729
WoS: 000564739400016
Scopus: 2-s2.0-85088982547
Institucija/grupa
IHTMTY - JOUR AU - Pavlović, Marijana AU - Tadić, Ana AU - Gligorijević, Nevenka AU - Poljarević, Jelena AU - Petrović, Tamara G. AU - Dojčinović, Biljana AU - Savić, Aleksandar AU - Radulović, Siniša PY - 2020 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/3713 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 G. and Dojčinović, Biljana and Savić, Aleksandar and Radulović, Siniša", 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. G., Dojčinović, B., Savić, A.,& Radulović, 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 TG, Dojčinović B, Savić A, Radulović 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 G., Dojčinović, Biljana, Savić, Aleksandar, Radulović, Siniša, "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 . .