Mononuclear gold(III) complexes with phenanthroline ligands as efficient inhibitors of angiogenesis: A comparative study with auranofin and sunitinib
Аутори
Pavić, AleksandarGlišić, Biljana
Vojnović, Sandra
Warzajtis, Beata
Savić, Nada D.
Antić, Marija
Radenković, Slavko
Janjić, Goran V.
Nikodinović-Runić, Jasmina
Rychlewska, Urszula
Djuran, Milos I.
Чланак у часопису (Рецензирана 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:
Phenanthroline / Gold(III) complexes / Embryotoxicity / Cytotoxicity / AngiogenesisИзвор:
Journal of Inorganic Biochemistry, 2017, 174, 156-168Издавач:
- Elsevier Science Inc, New York
Финансирање / пројекти:
- SupraMedChem"Balkans.Net SCOPES Institutional Partnership [IZ74Z0_160515]
- Синтеза нових комплекса метала и испитивање њихових реакција са пептидима (RS-MESTD-Basic Research (BR or ON)-172036)
- Изучавање микробиолошког диверзитета и карактеризација корисних срединских микроорганизама (RS-MESTD-Basic Research (BR or ON)-173048)
- Теорија графова и математичко програмирање са применама у хемији и рачунарству (RS-MESTD-Basic Research (BR or ON)-174033)
Напомена:
- This is the peer reviewed version of the paper: Pavić, A., Glišić, B., Vojnović, S., Warzajtis, B., Savić, N. D., Antić, M., Radenković, S., Janjić, G. V., Nikodinović-Runić, J., Rychlewska, U., & Djuran, M. I. (2017). Mononuclear gold(III) complexes with phenanthroline ligands as efficient inhibitors of angiogenesis: A comparative study with auranofin and sunitinib. Journal of Inorganic Biochemistry, 174, 156–168. https://doi.org/10.1016/j.jinorgbio.2017.06.009
- Relateds to published version: https://imagine.imgge.bg.ac.rs/handle/123456789/1011
Повезане информације:
- Друга верзија
https://doi.org/10.1016/j.jinorgbio.2017.06.009
DOI: 10.1016/j.jinorgbio.2017.06.009
ISSN: 0162-0134
PubMed: 28675847
WoS: 000406647700016
Scopus: 2-s2.0-85021674718
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Pavić, Aleksandar AU - Glišić, Biljana AU - Vojnović, Sandra AU - Warzajtis, Beata AU - Savić, Nada D. AU - Antić, Marija AU - Radenković, Slavko AU - Janjić, Goran V. AU - Nikodinović-Runić, Jasmina AU - Rychlewska, Urszula AU - Djuran, Milos I. PY - 2017 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1756 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 EP - 168 SP - 156 VL - 174 DO - 10.1016/j.jinorgbio.2017.06.009 ER -
@article{ author = "Pavić, Aleksandar and Glišić, Biljana and Vojnović, Sandra and Warzajtis, Beata and Savić, Nada D. and Antić, Marija and Radenković, Slavko and Janjić, Goran V. and Nikodinović-Runić, Jasmina and Rychlewska, Urszula and Djuran, Milos 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", pages = "168-156", volume = "174", doi = "10.1016/j.jinorgbio.2017.06.009" }
Pavić, A., Glišić, B., Vojnović, S., Warzajtis, B., Savić, N. D., Antić, M., Radenković, S., Janjić, G. V., Nikodinović-Runić, J., Rychlewska, U.,& Djuran, 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 B, Vojnović S, Warzajtis B, Savić ND, Antić M, Radenković S, Janjić GV, Nikodinović-Runić J, Rychlewska U, Djuran 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, Vojnović, Sandra, Warzajtis, Beata, Savić, Nada D., Antić, Marija, Radenković, Slavko, Janjić, Goran V., Nikodinović-Runić, Jasmina, Rychlewska, Urszula, Djuran, Milos 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 . .