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
Authors
Pantelić, Nebojša Đ.
Zmejkovski, Bojana

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

Trifunović, Srećko R.
Stanojković, Tatjana

Sabo, Tibor

Kaluđerović, Goran N.

Article (Accepted 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:
Apoptosis / Biological reactivity / Gold(III) complexes / Metal uptake / R 2 edda-type ligandsSource:
Journal of Inorganic Biochemistry, 2017, 172, 55-66Publisher:
- Elsevier
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:
- This is the peer-reviewed version of the following article: Pantelić, N.; Zmejkovski, B. B.; Kolundžija, B.; Crnogorac, M. Đ.; Vujić, J. M.; Dojčinović, B.; Trifunović, S. R.; Stanojković, T. P.; Sabo, T. J.; Kaluđerović, G. 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. Journal of Inorganic Biochemistry 2017, 172, 55–66. https://doi.org/10.1016/j.jinorgbio.2017.04.001
- http://cer.ihtm.bg.ac.rs/handle/123456789/2248
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
IHTMTY - JOUR AU - Pantelić, Nebojša Đ. AU - Zmejkovski, Bojana AU - Kolundžija, Branka AU - Crnogorac, Marija Đorđić AU - Vujić, Jelena M. AU - Dojčinović, Biljana AU - Trifunović, Srećko R. AU - Stanojković, Tatjana AU - Sabo, Tibor AU - Kaluđerović, Goran N. PY - 2017 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/2931 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 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 and Kolundžija, Branka and Crnogorac, Marija Đorđić and Vujić, Jelena M. and Dojčinović, Biljana 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", 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., Kolundžija, B., Crnogorac, M. Đ., Vujić, J. M., Dojčinović, B., 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., 172, 55-66. https://doi.org/10.1016/j.jinorgbio.2017.04.001
Pantelić NĐ, Zmejkovski B, Kolundžija B, Crnogorac MĐ, Vujić JM, Dojčinović B, 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, Kolundžija, Branka, Crnogorac, Marija Đorđić, Vujić, Jelena M., Dojčinović, Biljana, 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 . .