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
Autori
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.
Članak u časopisu (Recenzirana verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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.
Ključne reči:
Apoptosis / Biological reactivity / Gold(III) complexes / Metal uptake / R 2 edda-type ligandsIzvor:
Journal of Inorganic Biochemistry, 2017, 172, 55-66Izdavač:
- Elsevier Science Inc, New York
Finansiranje / projekti:
- Racionalni dizajn i sinteza biološki aktivnih i koordinacionih jedinjenja i funkcionalnih materijala, relevantnih u (bio)nanotehnologiji (RS-172035)
- Sinteza, modelovanje, fizičko-hemijske i biološke osobine organskih jedinjenja i odgovarajućih kompleksa metala (RS-172016)
- Modifikatori biološkog odgovora u fiziološkim i patološkim stanjima (RS-175011)
Napomena:
- 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
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3071
DOI: 10.1016/j.jinorgbio.2017.04.001
ISSN: 0162-0134
WoS: 000404000300007
Scopus: 2-s2.0-85017584556
Kolekcije
Institucija/grupa
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/123456789/3070 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 . .