Mononuclear gold(III) complexes with phenanthroline ligands as efficient inhibitors of angiogenesis: A comparative study with auranofin and sunitinib
Само за регистроване кориснике
2017
Аутори
Pavić, AleksandarGlišić, Biljana Đ.
Vojnović, Sandra
Warżajtis, Beata
Savić, Nada D.
Antić, Marija
Radenković, Slavko
Janjić, Goran V.
Nikodinović-Runić, Jasmina
Rychlewska, Urszula
Đuran, Miloš I.
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Gold(III) complexes with 1,7- and 4,7-phenanthroline ligands, [AuCl3(1,7-phen-kappa N7)] (1) and [AuCl3(4,7-phen-kappa N4)] (2) were synthesized and structurally characterized by spectroscopic (NMR, IR and UV-vis) and single crystal X-ray diffraction techniques. In these complexes, 1,7- and 4,7-phenanthrolines are monodentatedly coordinated to the Au(III) ion through the N7 and N4 nitrogen atoms, respectively. In comparison to the clinically relevant anti-angiogenic compounds auranofin and sunitinib, gold(III)-phenanthroline complexes showed from 1.5- to 20-fold higher anti-angiogenic potential, and 13- and 118-fold lower toxicity. Among the tested compounds, complex 1 was the most potent and may be an excellent anti-angiogenic drug candidate, since it showed strong anti-angiogenic activity in zebrafish embryos achieving IC50 value (concentration resulting in an anti-angiogenic phenotype at 50% of embryos) of 2.89 mu M, while had low toxicity with LC50 value (the concentration inducing... the lethal effect of 50% embryos) of 128 mu M. Molecular docking study revealed that both complexes and ligands could suppress angiogenesis targeting the multiple major regulators of angiogenesis, such as the vascular endothelial growth factor receptor (VEGFR-2), the matrix metalloproteases (MMP-2 and MMP-9), and thioredoxin reductase (TrxR1), where the complexes showed higher binding affinity in comparison to ligands, and particularly to auranofin, but comparable to sunitinib, an anti-angiogenic drug of clinical relevance.
Кључне речи:
Gold(III) complexes / Phenanthroline / Cytotoxicity / Embryotoxicity / AngiogenesisИзвор:
Journal of Inorganic Biochemistry, 2017, 174, 156-168Издавач:
- Elsevier Science Inc, New York
Финансирање / пројекти:
- Синтеза нових комплекса метала и испитивање њихових реакција са пептидима (RS-172036)
- Изучавање микробиолошког диверзитета и карактеризација корисних срединских микроорганизама (RS-173048)
- Теорија графова и математичко програмирање са применама у хемији и рачунарству (RS-174033)
- SupraMedChem'Balkans.Net SCOPES Institutional Partnership [IZ74Z0_160515]
Напомена:
- Peer-reviewed manuscript: http://cherry.chem.bg.ac.rs/handle/123456789/3110
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3111
DOI: 10.1016/j.jinorgbio.2017.06.009
ISSN: 0162-0134
PubMed: 28675847
WoS: 000406647700016
Scopus: 2-s2.0-85021674718
Колекције
Институција/група
Inovacioni centar / Innovation CentreTY - JOUR AU - Pavić, Aleksandar AU - Glišić, Biljana Đ. AU - Vojnović, Sandra AU - Warżajtis, Beata AU - Savić, Nada D. AU - Antić, Marija AU - Radenković, Slavko AU - Janjić, Goran V. AU - Nikodinović-Runić, Jasmina AU - Rychlewska, Urszula AU - Đuran, Miloš I. PY - 2017 UR - https://cherry.chem.bg.ac.rs/handle/123456789/2496 AB - Gold(III) complexes with 1,7- and 4,7-phenanthroline ligands, [AuCl3(1,7-phen-kappa N7)] (1) and [AuCl3(4,7-phen-kappa N4)] (2) were synthesized and structurally characterized by spectroscopic (NMR, IR and UV-vis) and single crystal X-ray diffraction techniques. In these complexes, 1,7- and 4,7-phenanthrolines are monodentatedly coordinated to the Au(III) ion through the N7 and N4 nitrogen atoms, respectively. In comparison to the clinically relevant anti-angiogenic compounds auranofin and sunitinib, gold(III)-phenanthroline complexes showed from 1.5- to 20-fold higher anti-angiogenic potential, and 13- and 118-fold lower toxicity. Among the tested compounds, complex 1 was the most potent and may be an excellent anti-angiogenic drug candidate, since it showed strong anti-angiogenic activity in zebrafish embryos achieving IC50 value (concentration resulting in an anti-angiogenic phenotype at 50% of embryos) of 2.89 mu M, while had low toxicity with LC50 value (the concentration inducing the lethal effect of 50% embryos) of 128 mu M. Molecular docking study revealed that both complexes and ligands could suppress angiogenesis targeting the multiple major regulators of angiogenesis, such as the vascular endothelial growth factor receptor (VEGFR-2), the matrix metalloproteases (MMP-2 and MMP-9), and thioredoxin reductase (TrxR1), where the complexes showed higher binding affinity in comparison to ligands, and particularly to auranofin, but comparable to sunitinib, an anti-angiogenic drug of clinical relevance. PB - Elsevier Science Inc, New York T2 - Journal of Inorganic Biochemistry T1 - Mononuclear gold(III) complexes with phenanthroline ligands as efficient inhibitors of angiogenesis: A comparative study with auranofin and sunitinib VL - 174 SP - 156 EP - 168 DO - 10.1016/j.jinorgbio.2017.06.009 ER -
@article{ author = "Pavić, Aleksandar and Glišić, Biljana Đ. and Vojnović, Sandra and Warżajtis, Beata and Savić, Nada D. and Antić, Marija and Radenković, Slavko and Janjić, Goran V. and Nikodinović-Runić, Jasmina and Rychlewska, Urszula and Đuran, Miloš I.", year = "2017", abstract = "Gold(III) complexes with 1,7- and 4,7-phenanthroline ligands, [AuCl3(1,7-phen-kappa N7)] (1) and [AuCl3(4,7-phen-kappa N4)] (2) were synthesized and structurally characterized by spectroscopic (NMR, IR and UV-vis) and single crystal X-ray diffraction techniques. In these complexes, 1,7- and 4,7-phenanthrolines are monodentatedly coordinated to the Au(III) ion through the N7 and N4 nitrogen atoms, respectively. In comparison to the clinically relevant anti-angiogenic compounds auranofin and sunitinib, gold(III)-phenanthroline complexes showed from 1.5- to 20-fold higher anti-angiogenic potential, and 13- and 118-fold lower toxicity. Among the tested compounds, complex 1 was the most potent and may be an excellent anti-angiogenic drug candidate, since it showed strong anti-angiogenic activity in zebrafish embryos achieving IC50 value (concentration resulting in an anti-angiogenic phenotype at 50% of embryos) of 2.89 mu M, while had low toxicity with LC50 value (the concentration inducing the lethal effect of 50% embryos) of 128 mu M. Molecular docking study revealed that both complexes and ligands could suppress angiogenesis targeting the multiple major regulators of angiogenesis, such as the vascular endothelial growth factor receptor (VEGFR-2), the matrix metalloproteases (MMP-2 and MMP-9), and thioredoxin reductase (TrxR1), where the complexes showed higher binding affinity in comparison to ligands, and particularly to auranofin, but comparable to sunitinib, an anti-angiogenic drug of clinical relevance.", publisher = "Elsevier Science Inc, New York", journal = "Journal of Inorganic Biochemistry", title = "Mononuclear gold(III) complexes with phenanthroline ligands as efficient inhibitors of angiogenesis: A comparative study with auranofin and sunitinib", volume = "174", pages = "156-168", doi = "10.1016/j.jinorgbio.2017.06.009" }
Pavić, A., Glišić, B. Đ., Vojnović, S., Warżajtis, B., Savić, N. D., Antić, M., Radenković, S., Janjić, G. V., Nikodinović-Runić, J., Rychlewska, U.,& Đuran, M. I.. (2017). Mononuclear gold(III) complexes with phenanthroline ligands as efficient inhibitors of angiogenesis: A comparative study with auranofin and sunitinib. in Journal of Inorganic Biochemistry Elsevier Science Inc, New York., 174, 156-168. https://doi.org/10.1016/j.jinorgbio.2017.06.009
Pavić A, Glišić BĐ, Vojnović S, Warżajtis B, Savić ND, Antić M, Radenković S, Janjić GV, Nikodinović-Runić J, Rychlewska U, Đuran MI. Mononuclear gold(III) complexes with phenanthroline ligands as efficient inhibitors of angiogenesis: A comparative study with auranofin and sunitinib. in Journal of Inorganic Biochemistry. 2017;174:156-168. doi:10.1016/j.jinorgbio.2017.06.009 .
Pavić, Aleksandar, Glišić, Biljana Đ., Vojnović, Sandra, Warżajtis, Beata, Savić, Nada D., Antić, Marija, Radenković, Slavko, Janjić, Goran V., Nikodinović-Runić, Jasmina, Rychlewska, Urszula, Đuran, Miloš I., "Mononuclear gold(III) complexes with phenanthroline ligands as efficient inhibitors of angiogenesis: A comparative study with auranofin and sunitinib" in Journal of Inorganic Biochemistry, 174 (2017):156-168, https://doi.org/10.1016/j.jinorgbio.2017.06.009 . .