In vitro antitumor activity, metal uptake and reactivity with ascorbic acid and BSA of some gold(III) complexes with N,N '-ethylenediamine bidentate ester ligands
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2017
Authors
Pantelić, Nebojša Đ.Zmejkovski, Bojana B.

Kolundžija, Branka
Crnogorac, Marija Đorđić
Vujić, Jelena M.
Dojčinović, Biljana P.

Trifunović, Srećko R.

Stanojković, Tatjana

Sabo, Tibor

Kaluđerović, Goran N.

Article (Published version)

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Four novel gold(III) complexes of general formulae [AuCl2{(S,S)-R(2)eddl}]PF6 (R(2)eddl = O,O'-dialkyl-(S,S)-ethylenediamine-N,N'-di-2-(4-methyl)pentanoate, R= n-Pr, n-Bu, n-Pe, i-Bu; 1-4, respectively), were synthesized and characterized by elemental analysis, UV/Vis, IR, and NMR spectroscopy, as well as high resolution mass spectrometry. Density functional theory calculations pointed out that (R,R)-N,N'-configuration diastereoisomers were energetically the most favorable. Duo to high cytotoxic activity complex 3 was chosen for stability study in DMSO, no decomposition occurs within 24 h, and for the reaction with ascorbic acid in which was reduced immediately. Additionally, 3 interacts with bovine serum albumin (BSA) as proven by UV/Vis spectroscopy. In vitro antitumor activity was determined against human cervix adenocarcinoma (HeLa), human myelogenous leukemia (K562), and human melanoma (Fem-x) cancer cell lines, as well as against non-cancerous human embryonic lung fibroblast cell...s MRC-5. The highest activity was observed against K562 cells (IC50: 5.04-6.51 mu M). Selectivity indices showed that these complexes are less toxic than cisplatin. 3 had a similar viability kinetics on HeLa cells as cisplatin. Drug accumulation studies in HeLa cells showed that the total gold uptake increased much faster than that of cisplatin pointing out that 3 more efficiently enters the cells than cisplatin. Furthermore, morphological and cell cycle analysis reveal that gold(III) complexes induced apoptosis in time- and dose-dependent manner.
Keywords:
Gold(III) complexes / R(2)edda-type ligands / Metal uptake / Apoptosis / Biological reactivitySource:
Journal of Inorganic Biochemistry, 2017, 172, 55-66Publisher:
- Elsevier Science Inc, New York
Funding / projects:
- Rational design and synthesis of biologically active and coordination compounds and functional materials, relevant for (bio)nanotechnology (RS-172035)
- Synthesis, modeling, physicochemical and biological properties of organic compounds and related metal complexes (RS-172016)
- Biological response modifiers in physiological and pathological conditions (RS-175011)
Note:
- Peer-reviewed manuscript: http://cherry.chem.bg.ac.rs/handle/123456789/3070
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3071
DOI: 10.1016/j.jinorgbio.2017.04.001
ISSN: 0162-0134
PubMed: 28433833
WoS: 000404000300007
Scopus: 2-s2.0-85017584556
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Institution/Community
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Pantelić, Nebojša Đ. AU - Zmejkovski, Bojana B. AU - Kolundžija, Branka AU - Crnogorac, Marija Đorđić AU - Vujić, Jelena M. AU - Dojčinović, Biljana P. AU - Trifunović, Srećko R. AU - Stanojković, Tatjana AU - Sabo, Tibor AU - Kaluđerović, Goran N. PY - 2017 UR - https://cherry.chem.bg.ac.rs/handle/123456789/2478 AB - Four novel gold(III) complexes of general formulae [AuCl2{(S,S)-R(2)eddl}]PF6 (R(2)eddl = O,O'-dialkyl-(S,S)-ethylenediamine-N,N'-di-2-(4-methyl)pentanoate, R= n-Pr, n-Bu, n-Pe, i-Bu; 1-4, respectively), were synthesized and characterized by elemental analysis, UV/Vis, IR, and NMR spectroscopy, as well as high resolution mass spectrometry. Density functional theory calculations pointed out that (R,R)-N,N'-configuration diastereoisomers were energetically the most favorable. Duo to high cytotoxic activity complex 3 was chosen for stability study in DMSO, no decomposition occurs within 24 h, and for the reaction with ascorbic acid in which was reduced immediately. Additionally, 3 interacts with bovine serum albumin (BSA) as proven by UV/Vis spectroscopy. In vitro antitumor activity was determined against human cervix adenocarcinoma (HeLa), human myelogenous leukemia (K562), and human melanoma (Fem-x) cancer cell lines, as well as against non-cancerous human embryonic lung fibroblast cells MRC-5. The highest activity was observed against K562 cells (IC50: 5.04-6.51 mu M). Selectivity indices showed that these complexes are less toxic than cisplatin. 3 had a similar viability kinetics on HeLa cells as cisplatin. Drug accumulation studies in HeLa cells showed that the total gold uptake increased much faster than that of cisplatin pointing out that 3 more efficiently enters the cells than cisplatin. Furthermore, morphological and cell cycle analysis reveal that gold(III) complexes induced apoptosis in time- and dose-dependent manner. PB - Elsevier Science Inc, New York T2 - Journal of Inorganic Biochemistry T1 - In vitro antitumor activity, metal uptake and reactivity with ascorbic acid and BSA of some gold(III) complexes with N,N '-ethylenediamine bidentate ester ligands VL - 172 SP - 55 EP - 66 DO - 10.1016/j.jinorgbio.2017.04.001 ER -
@article{ author = "Pantelić, Nebojša Đ. and Zmejkovski, Bojana B. and Kolundžija, Branka and Crnogorac, Marija Đorđić and Vujić, Jelena M. and Dojčinović, Biljana P. and Trifunović, Srećko R. and Stanojković, Tatjana and Sabo, Tibor and Kaluđerović, Goran N.", year = "2017", abstract = "Four novel gold(III) complexes of general formulae [AuCl2{(S,S)-R(2)eddl}]PF6 (R(2)eddl = O,O'-dialkyl-(S,S)-ethylenediamine-N,N'-di-2-(4-methyl)pentanoate, R= n-Pr, n-Bu, n-Pe, i-Bu; 1-4, respectively), were synthesized and characterized by elemental analysis, UV/Vis, IR, and NMR spectroscopy, as well as high resolution mass spectrometry. Density functional theory calculations pointed out that (R,R)-N,N'-configuration diastereoisomers were energetically the most favorable. Duo to high cytotoxic activity complex 3 was chosen for stability study in DMSO, no decomposition occurs within 24 h, and for the reaction with ascorbic acid in which was reduced immediately. Additionally, 3 interacts with bovine serum albumin (BSA) as proven by UV/Vis spectroscopy. In vitro antitumor activity was determined against human cervix adenocarcinoma (HeLa), human myelogenous leukemia (K562), and human melanoma (Fem-x) cancer cell lines, as well as against non-cancerous human embryonic lung fibroblast cells MRC-5. The highest activity was observed against K562 cells (IC50: 5.04-6.51 mu M). Selectivity indices showed that these complexes are less toxic than cisplatin. 3 had a similar viability kinetics on HeLa cells as cisplatin. Drug accumulation studies in HeLa cells showed that the total gold uptake increased much faster than that of cisplatin pointing out that 3 more efficiently enters the cells than cisplatin. Furthermore, morphological and cell cycle analysis reveal that gold(III) complexes induced apoptosis in time- and dose-dependent manner.", publisher = "Elsevier Science Inc, New York", journal = "Journal of Inorganic Biochemistry", title = "In vitro antitumor activity, metal uptake and reactivity with ascorbic acid and BSA of some gold(III) complexes with N,N '-ethylenediamine bidentate ester ligands", volume = "172", pages = "55-66", doi = "10.1016/j.jinorgbio.2017.04.001" }
Pantelić, N. Đ., Zmejkovski, B. B., Kolundžija, B., Crnogorac, M. Đ., Vujić, J. M., Dojčinović, B. P., Trifunović, S. R., Stanojković, T., Sabo, T.,& Kaluđerović, G. N.. (2017). In vitro antitumor activity, metal uptake and reactivity with ascorbic acid and BSA of some gold(III) complexes with N,N '-ethylenediamine bidentate ester ligands. in Journal of Inorganic Biochemistry Elsevier Science Inc, New York., 172, 55-66. https://doi.org/10.1016/j.jinorgbio.2017.04.001
Pantelić NĐ, Zmejkovski BB, Kolundžija B, Crnogorac MĐ, Vujić JM, Dojčinović BP, Trifunović SR, Stanojković T, Sabo T, Kaluđerović GN. In vitro antitumor activity, metal uptake and reactivity with ascorbic acid and BSA of some gold(III) complexes with N,N '-ethylenediamine bidentate ester ligands. in Journal of Inorganic Biochemistry. 2017;172:55-66. doi:10.1016/j.jinorgbio.2017.04.001 .
Pantelić, Nebojša Đ., Zmejkovski, Bojana B., Kolundžija, Branka, Crnogorac, Marija Đorđić, Vujić, Jelena M., Dojčinović, Biljana P., Trifunović, Srećko R., Stanojković, Tatjana, Sabo, Tibor, Kaluđerović, Goran N., "In vitro antitumor activity, metal uptake and reactivity with ascorbic acid and BSA of some gold(III) complexes with N,N '-ethylenediamine bidentate ester ligands" in Journal of Inorganic Biochemistry, 172 (2017):55-66, https://doi.org/10.1016/j.jinorgbio.2017.04.001 . .