Antiglioma activity of GoPI-sugar, a novel gold(I)-phosphole inhibitor: Chemical synthesis, mechanistic studies, and effectiveness in vivo
Glioblastoma, an aggressive brain tumor, has a poor prognosis and a high risk of recurrence. An improved chemotherapeutic approach is required to complement radiation therapy. Gold(I) complexes bearing phosphole ligands are promising agents in the treatment of cancer and disturb the redox balance an...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
16 January 2014
|
| In: |
Biochimica et biophysica acta. Proteins and proteomics
Year: 2014, Volume: 1844, Issue: 8, Pages: 1415-1426 |
| ISSN: | 1878-1454 |
| DOI: | 10.1016/j.bbapap.2014.01.006 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.bbapap.2014.01.006 Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S1570963914000090 
|
| Author Notes: | E. Jortzik, M. Farhadi, R. Ahmadi, K. Tóth, J. Lohr, B.M. Helmke, S. Kehr, A. Unterberg, I. Ott, R. Gust, V. Deborde, E. Davioud-Charvet, R. Réau, K. Becker, C. Herold-Mende |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1725683792 | ||
| 003 | DE-627 | ||
| 005 | 20230426183834.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 200728s2014 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.bbapap.2014.01.006 |2 doi | |
| 035 | |a (DE-627)1725683792 | ||
| 035 | |a (DE-599)KXP1725683792 | ||
| 035 | |a (OCoLC)1341348615 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Jortzik, Esther |e VerfasserIn |0 (DE-588)1020040734 |0 (DE-627)687746612 |0 (DE-576)359435580 |4 aut | |
| 245 | 1 | 0 | |a Antiglioma activity of GoPI-sugar, a novel gold(I)-phosphole inhibitor |b Chemical synthesis, mechanistic studies, and effectiveness in vivo |c E. Jortzik, M. Farhadi, R. Ahmadi, K. Tóth, J. Lohr, B.M. Helmke, S. Kehr, A. Unterberg, I. Ott, R. Gust, V. Deborde, E. Davioud-Charvet, R. Réau, K. Becker, C. Herold-Mende |
| 264 | 1 | |c 16 January 2014 | |
| 300 | |a 12 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 28.07.2020 | ||
| 520 | |a Glioblastoma, an aggressive brain tumor, has a poor prognosis and a high risk of recurrence. An improved chemotherapeutic approach is required to complement radiation therapy. Gold(I) complexes bearing phosphole ligands are promising agents in the treatment of cancer and disturb the redox balance and proliferation of cancer cells by inhibiting disulfide reductases. Here, we report on the antitumor properties of the gold(I) complex 1-phenyl-bis(2-pyridyl)phosphole gold chloride thio-β-d-glucose tetraacetate (GoPI-sugar), which exhibits antiproliferative effects on human (NCH82, NCH89) and rat (C6) glioma cell lines. Compared to carmustine (BCNU), an established nitrosourea compound for the treatment of glioblastomas that inhibits the proliferation of these glioma cell lines with an IC50 of 430μM, GoPI-sugar is more effective by two orders of magnitude. Moreover, GoPI-sugar inhibits malignant glioma growth in vivo in a C6 glioma rat model and significantly reduces tumor volume while being well tolerated. Both the gold(I) chloro- and thiosugar-substituted phospholes interact with DNA albeit more weakly for the latter. Furthermore, GoPI-sugar irreversibly and potently inhibits thioredoxin reductase (IC50 4.3nM) and human glutathione reductase (IC50 88.5nM). However, treatment with GoPI-sugar did not significantly alter redox parameters in the brain tissue of treated animals. This might be due to compensatory upregulation of redox-related enzymes but might also indicate that the antiproliferative effects of GoPI-sugar in vivo are rather based on DNA interaction and inhibition of topoisomerase I than on the disturbance of redox equilibrium. Since GoPI-sugar is highly effective against glioblastomas and well tolerated, it represents a most promising lead for drug development. This article is part of a Special Issue entitled: Thiol-Based Redox Processes. | ||
| 650 | 4 | |a Cancer | |
| 650 | 4 | |a Glioblastoma | |
| 650 | 4 | |a Glutathione reductase | |
| 650 | 4 | |a Gold(I)-phosphole complex | |
| 650 | 4 | |a Redox system | |
| 650 | 4 | |a Thioredoxin reductase | |
| 700 | 1 | |a Ahmadi, Rezvan |d 1967- |e VerfasserIn |0 (DE-588)123535921 |0 (DE-627)706337158 |0 (DE-576)293755027 |4 aut | |
| 700 | 1 | |a Helmke, Burkhard Maria |d 1964- |e VerfasserIn |0 (DE-588)124280269 |0 (DE-627)08575806X |0 (DE-576)294100083 |4 aut | |
| 700 | 1 | |a Unterberg, Andreas |e VerfasserIn |0 (DE-588)1032681187 |0 (DE-627)738641200 |0 (DE-576)168441233 |4 aut | |
| 700 | 1 | |a Herold-Mende, Christel |e VerfasserIn |0 (DE-588)1022936549 |0 (DE-627)717335577 |0 (DE-576)366194267 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Biochimica et biophysica acta. Proteins and proteomics |d Amsterdam [u.a.] : [Verlag nicht ermittelbar], 2002 |g 1844(2014), 8, Seite 1415-1426 |h Online-Ressource |w (DE-627)50292442X |w (DE-600)2209540-8 |w (DE-576)251822702 |x 1878-1454 |7 nnas |a Antiglioma activity of GoPI-sugar, a novel gold(I)-phosphole inhibitor Chemical synthesis, mechanistic studies, and effectiveness in vivo |
| 773 | 1 | 8 | |g volume:1844 |g year:2014 |g number:8 |g pages:1415-1426 |g extent:12 |a Antiglioma activity of GoPI-sugar, a novel gold(I)-phosphole inhibitor Chemical synthesis, mechanistic studies, and effectiveness in vivo |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.bbapap.2014.01.006 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u http://www.sciencedirect.com/science/article/pii/S1570963914000090 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20200728 | ||
| 993 | |a Article | ||
| 994 | |a 2014 | ||
| 998 | |g 1022936549 |a Herold-Mende, Christel |m 1022936549:Herold-Mende, Christel |d 910000 |d 911200 |e 910000PH1022936549 |e 911200PH1022936549 |k 0/910000/ |k 1/910000/911200/ |p 15 |y j | ||
| 998 | |g 1032681187 |a Unterberg, Andreas |m 1032681187:Unterberg, Andreas |d 910000 |d 911200 |e 910000PU1032681187 |e 911200PU1032681187 |k 0/910000/ |k 1/910000/911200/ |p 8 | ||
| 998 | |g 124280269 |a Helmke, Burkhard Maria |m 124280269:Helmke, Burkhard Maria |d 50000 |e 50000PH124280269 |k 0/50000/ |p 6 | ||
| 998 | |g 123535921 |a Ahmadi, Rezvan |m 123535921:Ahmadi, Rezvan |d 910000 |d 911200 |e 910000PA123535921 |e 911200PA123535921 |k 0/910000/ |k 1/910000/911200/ |p 3 | ||
| 999 | |a KXP-PPN1725683792 |e 3730975862 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"name":{"displayForm":["E. Jortzik, M. Farhadi, R. Ahmadi, K. Tóth, J. Lohr, B.M. Helmke, S. Kehr, A. Unterberg, I. Ott, R. Gust, V. Deborde, E. Davioud-Charvet, R. Réau, K. Becker, C. Herold-Mende"]},"origin":[{"dateIssuedDisp":"16 January 2014","dateIssuedKey":"2014"}],"recId":"1725683792","id":{"doi":["10.1016/j.bbapap.2014.01.006"],"eki":["1725683792"]},"type":{"media":"Online-Ressource","bibl":"article-journal"},"person":[{"display":"Jortzik, Esther","family":"Jortzik","role":"aut","given":"Esther"},{"given":"Rezvan","family":"Ahmadi","role":"aut","display":"Ahmadi, Rezvan"},{"given":"Burkhard Maria","role":"aut","family":"Helmke","display":"Helmke, Burkhard Maria"},{"display":"Unterberg, Andreas","role":"aut","family":"Unterberg","given":"Andreas"},{"given":"Christel","display":"Herold-Mende, Christel","role":"aut","family":"Herold-Mende"}],"note":["Gesehen am 28.07.2020"],"language":["eng"],"physDesc":[{"extent":"12 S."}],"title":[{"subtitle":"Chemical synthesis, mechanistic studies, and effectiveness in vivo","title_sort":"Antiglioma activity of GoPI-sugar, a novel gold(I)-phosphole inhibitor","title":"Antiglioma activity of GoPI-sugar, a novel gold(I)-phosphole inhibitor"}],"relHost":[{"physDesc":[{"extent":"Online-Ressource"}],"title":[{"title_sort":"Biochimica et biophysica acta","subtitle":"BBA","title":"Biochimica et biophysica acta","partname":"Proteins and proteomics"}],"part":{"year":"2014","pages":"1415-1426","issue":"8","extent":"12","text":"1844(2014), 8, Seite 1415-1426","volume":"1844"},"note":["Gesehen am 08.01.2020","Bis 2016 Bände zugleich Bände von: Biochimica et biophysica acta"],"pubHistory":["1598.2002 -"],"titleAlt":[{"title":"Biochimica et biophysica acta / Proteins and proteomics"}],"language":["eng"],"disp":"Antiglioma activity of GoPI-sugar, a novel gold(I)-phosphole inhibitor Chemical synthesis, mechanistic studies, and effectiveness in vivoBiochimica et biophysica acta. Proteins and proteomics","origin":[{"publisher":"[Verlag nicht ermittelbar]","dateIssuedDisp":"2002-","publisherPlace":"Amsterdam [u.a.]","dateIssuedKey":"2002"}],"recId":"50292442X","id":{"issn":["1878-1454"],"zdb":["2209540-8"],"eki":["50292442X"]},"type":{"bibl":"periodical","media":"Online-Ressource"}}]} | ||
| SRT | |a JORTZIKESTANTIGLIOMA1620 | ||