Synthesis, characterization, biological activity, DNA and BSA binding study: novel copper(II) complexes with 2-hydroxy-4-aryl-4-oxo-2-butenoate
Само за регистроване кориснике
2016
Аутори
Joksimović, NenadBaskic, Dejan
Popovic, Suzana
Zarić, Milan
Kosanić, Marijana
Ranković, Branislav
Stanojković, Tatjana P.
Novaković, Slađana B.
Davidovic, Goran
Bugarčič, Zorica M.
Janković, Nenad
Чланак у часопису (Објављена верзија)
,
© The Royal Society of Chemistry 2016
Метаподаци
Приказ свих података о документуАпстракт
A serie of novel square pyramidal copper(II) complexes [Cu(L)(2)H2O] (3a-d) with O,O-bidentate ligands [L = ethyl-2-hydroxy-4-aryl-4-oxo-2-butenoate; aryl = 3-methoxyphenyl-2a, (E)-2-phenylvinyl-2b, (E)-2-(4-hydroxy-3-methoxyphenyl)vinyl-2c, 3-nitrophenyl-2d, 2-thienyl-2e] were synthesized and characterized by spectral (UV-Vis, IR, ESI-MS and EPR), elemental and X-ray analysis. The antimicrobial activity was estimated by the determination of the minimal inhibitory concentration (MIC) using the broth micro-dilution method. The most active antibacterial compounds were 3c and 3d, while the best antifungal activity was showed by complexes 3b and 3e. The lowest MIC value (0.048 mg mL(-1)) was measured for 3c against Proteus mirabilis. The cytotoxic activity was tested using the MTT method on human epithelial carcinoma HeLa cells, human lung carcinoma A549 cells and human colon carcinoma LS174 cells. All complexes showed extremely better cytotoxic activity compared to cisplatin at all tested... concentrations. Compound 3d expressed the best activity against all tested cell lines with IC50 values ranging from 7.45 to 7.91 mu g mL(-1). The type of cell death and the impact on the cell cycle for 3d and 3e were evaluated by flow cytometry. Both compounds induced apoptosis and S phase cell cycle arrest. The interactions between selected complexes (3d and 3e) and CT-DNA or bovine serum albumin (BSA) were investigated by the fluorescence spectroscopic method. Competitive experiments with ethidium bromide (EB) indicated that 3d and 3e have a propensity to displace EB from the EB-DNA complex through intercalation suggesting strong competition with EB [K-sv = (1.4 +/- 0.2) and (2.9 +/- 0.1) x 10(4) M-1, respectively]. K-sv values indicate that these complexes bind to DNA covalently and non-covalently. The achieved results in the fluorescence titration of BSA with 3d and 3e [K-a = (2.9 +/- 0.2) x 10(6) and (2.5 +/- 0.2) x 10(5) M, respectively] showed that the fluorescence quenching of BSA is a result of the formation of the 3d- and 3e-BSA complexes. The obtained K-a values are high enough to ensure that a significant amount of 3d and 3e gets transported and distributed through the cells.
Извор:
Dalton Transactions, 2016, 45, 38, 15067-15077Финансирање / пројекти:
- Испитивање механизма реакција комплекса јона прелазних метала са биолошки значајним молекулима (RS-MESTD-Basic Research (BR or ON)-172011)
DOI: 10.1039/c6dt02257j
ISSN: 1477-9226; 1477-9234
PubMed: 27711668
WoS: 000385198400025
Scopus: 2-s2.0-84989966778
Колекције
Институција/група
VinčaTY - JOUR AU - Joksimović, Nenad AU - Baskic, Dejan AU - Popovic, Suzana AU - Zarić, Milan AU - Kosanić, Marijana AU - Ranković, Branislav AU - Stanojković, Tatjana P. AU - Novaković, Slađana B. AU - Davidovic, Goran AU - Bugarčič, Zorica M. AU - Janković, Nenad PY - 2016 UR - https://vinar.vin.bg.ac.rs/handle/123456789/1269 AB - A serie of novel square pyramidal copper(II) complexes [Cu(L)(2)H2O] (3a-d) with O,O-bidentate ligands [L = ethyl-2-hydroxy-4-aryl-4-oxo-2-butenoate; aryl = 3-methoxyphenyl-2a, (E)-2-phenylvinyl-2b, (E)-2-(4-hydroxy-3-methoxyphenyl)vinyl-2c, 3-nitrophenyl-2d, 2-thienyl-2e] were synthesized and characterized by spectral (UV-Vis, IR, ESI-MS and EPR), elemental and X-ray analysis. The antimicrobial activity was estimated by the determination of the minimal inhibitory concentration (MIC) using the broth micro-dilution method. The most active antibacterial compounds were 3c and 3d, while the best antifungal activity was showed by complexes 3b and 3e. The lowest MIC value (0.048 mg mL(-1)) was measured for 3c against Proteus mirabilis. The cytotoxic activity was tested using the MTT method on human epithelial carcinoma HeLa cells, human lung carcinoma A549 cells and human colon carcinoma LS174 cells. All complexes showed extremely better cytotoxic activity compared to cisplatin at all tested concentrations. Compound 3d expressed the best activity against all tested cell lines with IC50 values ranging from 7.45 to 7.91 mu g mL(-1). The type of cell death and the impact on the cell cycle for 3d and 3e were evaluated by flow cytometry. Both compounds induced apoptosis and S phase cell cycle arrest. The interactions between selected complexes (3d and 3e) and CT-DNA or bovine serum albumin (BSA) were investigated by the fluorescence spectroscopic method. Competitive experiments with ethidium bromide (EB) indicated that 3d and 3e have a propensity to displace EB from the EB-DNA complex through intercalation suggesting strong competition with EB [K-sv = (1.4 +/- 0.2) and (2.9 +/- 0.1) x 10(4) M-1, respectively]. K-sv values indicate that these complexes bind to DNA covalently and non-covalently. The achieved results in the fluorescence titration of BSA with 3d and 3e [K-a = (2.9 +/- 0.2) x 10(6) and (2.5 +/- 0.2) x 10(5) M, respectively] showed that the fluorescence quenching of BSA is a result of the formation of the 3d- and 3e-BSA complexes. The obtained K-a values are high enough to ensure that a significant amount of 3d and 3e gets transported and distributed through the cells. T2 - Dalton Transactions T1 - Synthesis, characterization, biological activity, DNA and BSA binding study: novel copper(II) complexes with 2-hydroxy-4-aryl-4-oxo-2-butenoate VL - 45 IS - 38 SP - 15067 EP - 15077 DO - 10.1039/c6dt02257j ER -
@article{ author = "Joksimović, Nenad and Baskic, Dejan and Popovic, Suzana and Zarić, Milan and Kosanić, Marijana and Ranković, Branislav and Stanojković, Tatjana P. and Novaković, Slađana B. and Davidovic, Goran and Bugarčič, Zorica M. and Janković, Nenad", year = "2016", abstract = "A serie of novel square pyramidal copper(II) complexes [Cu(L)(2)H2O] (3a-d) with O,O-bidentate ligands [L = ethyl-2-hydroxy-4-aryl-4-oxo-2-butenoate; aryl = 3-methoxyphenyl-2a, (E)-2-phenylvinyl-2b, (E)-2-(4-hydroxy-3-methoxyphenyl)vinyl-2c, 3-nitrophenyl-2d, 2-thienyl-2e] were synthesized and characterized by spectral (UV-Vis, IR, ESI-MS and EPR), elemental and X-ray analysis. The antimicrobial activity was estimated by the determination of the minimal inhibitory concentration (MIC) using the broth micro-dilution method. The most active antibacterial compounds were 3c and 3d, while the best antifungal activity was showed by complexes 3b and 3e. The lowest MIC value (0.048 mg mL(-1)) was measured for 3c against Proteus mirabilis. The cytotoxic activity was tested using the MTT method on human epithelial carcinoma HeLa cells, human lung carcinoma A549 cells and human colon carcinoma LS174 cells. All complexes showed extremely better cytotoxic activity compared to cisplatin at all tested concentrations. Compound 3d expressed the best activity against all tested cell lines with IC50 values ranging from 7.45 to 7.91 mu g mL(-1). The type of cell death and the impact on the cell cycle for 3d and 3e were evaluated by flow cytometry. Both compounds induced apoptosis and S phase cell cycle arrest. The interactions between selected complexes (3d and 3e) and CT-DNA or bovine serum albumin (BSA) were investigated by the fluorescence spectroscopic method. Competitive experiments with ethidium bromide (EB) indicated that 3d and 3e have a propensity to displace EB from the EB-DNA complex through intercalation suggesting strong competition with EB [K-sv = (1.4 +/- 0.2) and (2.9 +/- 0.1) x 10(4) M-1, respectively]. K-sv values indicate that these complexes bind to DNA covalently and non-covalently. The achieved results in the fluorescence titration of BSA with 3d and 3e [K-a = (2.9 +/- 0.2) x 10(6) and (2.5 +/- 0.2) x 10(5) M, respectively] showed that the fluorescence quenching of BSA is a result of the formation of the 3d- and 3e-BSA complexes. The obtained K-a values are high enough to ensure that a significant amount of 3d and 3e gets transported and distributed through the cells.", journal = "Dalton Transactions", title = "Synthesis, characterization, biological activity, DNA and BSA binding study: novel copper(II) complexes with 2-hydroxy-4-aryl-4-oxo-2-butenoate", volume = "45", number = "38", pages = "15067-15077", doi = "10.1039/c6dt02257j" }
Joksimović, N., Baskic, D., Popovic, S., Zarić, M., Kosanić, M., Ranković, B., Stanojković, T. P., Novaković, S. B., Davidovic, G., Bugarčič, Z. M.,& Janković, N.. (2016). Synthesis, characterization, biological activity, DNA and BSA binding study: novel copper(II) complexes with 2-hydroxy-4-aryl-4-oxo-2-butenoate. in Dalton Transactions, 45(38), 15067-15077. https://doi.org/10.1039/c6dt02257j
Joksimović N, Baskic D, Popovic S, Zarić M, Kosanić M, Ranković B, Stanojković TP, Novaković SB, Davidovic G, Bugarčič ZM, Janković N. Synthesis, characterization, biological activity, DNA and BSA binding study: novel copper(II) complexes with 2-hydroxy-4-aryl-4-oxo-2-butenoate. in Dalton Transactions. 2016;45(38):15067-15077. doi:10.1039/c6dt02257j .
Joksimović, Nenad, Baskic, Dejan, Popovic, Suzana, Zarić, Milan, Kosanić, Marijana, Ranković, Branislav, Stanojković, Tatjana P., Novaković, Slađana B., Davidovic, Goran, Bugarčič, Zorica M., Janković, Nenad, "Synthesis, characterization, biological activity, DNA and BSA binding study: novel copper(II) complexes with 2-hydroxy-4-aryl-4-oxo-2-butenoate" in Dalton Transactions, 45, no. 38 (2016):15067-15077, https://doi.org/10.1039/c6dt02257j . .