Synthesis, chemical characterization, PARP inhibition, DNA binding and cellular uptake of novel ruthenium(II)-arene complexes bearing benzamide derivatives in human breast cancer cells
Authorized Users Only
2020
Authors
Pavlović, MarijanaTadić, Ana
Gligorijević, Nevenka
Poljarević, Jelena
Petrović, Tamara G.
Dojčinović, Biljana
Savić, Aleksandar
Radulović, Siniša
Article (Published version)
,
Elsevier
Metadata
Show full item recordAbstract
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.
Keywords:
Antitumor agents / Breast cancer / PARP inhibitor / Ruthenium(II)Source:
Journal of Inorganic Biochemistry, 2020, 210, 111155-Publisher:
- Elsevier
Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200168 (University of Belgrade, Faculty of Chemistry) (RS-MESTD-inst-2020-200168)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200043 (Institute of Oncology and Radiology of Serbia, Belgrade) (RS-MESTD-inst-2020-200043)
Note:
- The peer-reviewed version: https://cer.ihtm.bg.ac.rs/handle/123456789/3713
DOI: 10.1016/j.jinorgbio.2020.111155
ISSN: 0162-0134
PubMed: 32768729
WoS: 000564739400016
Scopus: 2-s2.0-85088982547
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Institution/Community
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/123456789/3634 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 . .