Comparative in vitro and in vivo pharmacological investigation of platinum(IV) complexes as novel anticancer drug candidates for oral application
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| 024 | 7 | 0 | |a 10.1007/s00775-014-1214-6 |2 doi |
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| 245 | 0 | 0 | |a Comparative in vitro and in vivo pharmacological investigation of platinum(IV) complexes as novel anticancer drug candidates for oral application |h [Elektronische Daten] |c [Sarah Theiner, Hristo Varbanov, Markus Galanski, Alexander Egger, Walter Berger, Petra Heffeter, Bernhard Keppler] |
| 520 | 3 | |a Platinum(IV) complexes are promising candidates as prodrugs for oral application in anticancer chemotherapy. However, only a few Pt(IV) compounds entered (pre)clinical trials, e.g. satraplatin, while most of the others were only tested in vitro.Aim of the study was investigation of the in vivo pharmacological behavior as well as the anticancer activity of two novel platinum(IV) complexes vs. satraplatin. The drugs were selected due to significantly different in vitro cytotoxicity while sharing some physicochemical properties (e.g. lipophilicity). Initial experiments indicated that the highly in vitro cytotoxic compound1 ((OC-6-33)-dichloridobis((4-ethoxy)-4-oxobutanoato)-bis(ethylamine)platinum(IV)) was also characterized by high drug absorption and tissue platinum levels after oral application. Interestingly, analysis of serum samples using SEC-ICP-MS revealed that the administered drugs havecompletely been metabolized and/or bound to proteinsin serum within 2h after treatment. With regard to the activity in vivo, the outcomes were rather unexpected: although potent anticancer effect of 1 was observed in cell culture, the effects in vivo were rather minor. Nevertheless, 1 was superior to 2 ((OC-6-33)-diammine(cyclobutane-1,1-dicarboxylato)-bis((4-cyclopentylamino)-4-oxobutanoato)platinum(IV)) after i.p. administration, which was, at least to some extent, in accordance to the cell culture experiments. After oral gavage, both compounds exhibited comparable activity. This is remarkable considering the distinctly lower activity of 2 in cell culture as well as the low platinum levels detected both in serum and tissues after oral application. Consequently, our data indicate that the prediction of in vivo anticancer activity by cell culture experiments is not trivial, especially for orally applied drugs. Graphical Abstract: | |
| 540 | |a SBIC, 2014 | ||
| 690 | 7 | |a Platinum(IV) complexes |2 nationallicence | |
| 690 | 7 | |a Anticancer activity |2 nationallicence | |
| 690 | 7 | |a ICP-MS |2 nationallicence | |
| 690 | 7 | |a Oral administration |2 nationallicence | |
| 700 | 1 | |a Theiner |D Sarah |u Institute of Inorganic Chemistry, University of Vienna, Waehringer Strasse 42, 1090, Vienna, Austria |4 aut | |
| 700 | 1 | |a Varbanov |D Hristo |u Institute of Inorganic Chemistry, University of Vienna, Waehringer Strasse 42, 1090, Vienna, Austria |4 aut | |
| 700 | 1 | |a Galanski |D Markus |u Institute of Inorganic Chemistry, University of Vienna, Waehringer Strasse 42, 1090, Vienna, Austria |4 aut | |
| 700 | 1 | |a Egger |D Alexander |u ADSI-Austrian Drug Screening Institute GmbH, Innrain 66a, 6020, Innsbruck, Austria |4 aut | |
| 700 | 1 | |a Berger |D Walter |u Research Platform ‘Translational Cancer Therapy Research', University of Vienna, Waehringer Strasse 42, 1090, Vienna, Austria |4 aut | |
| 700 | 1 | |a Heffeter |D Petra |u Research Platform ‘Translational Cancer Therapy Research', University of Vienna, Waehringer Strasse 42, 1090, Vienna, Austria |4 aut | |
| 700 | 1 | |a Keppler |D Bernhard |u Institute of Inorganic Chemistry, University of Vienna, Waehringer Strasse 42, 1090, Vienna, Austria |4 aut | |
| 773 | 0 | |t JBIC Journal of Biological Inorganic Chemistry |d Springer Berlin Heidelberg |g 20/1(2015-01-01), 89-99 |x 0949-8257 |q 20:1<89 |1 2015 |2 20 |o 775 | |
| 856 | 4 | 0 | |u https://doi.org/10.1007/s00775-014-1214-6 |q text/html |z Onlinezugriff via DOI |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 900 | 7 | |a Metadata rights reserved |b Springer special CC-BY-NC licence |2 nationallicence | |
| 908 | |D 1 |a research-article |2 jats | ||
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| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1007/s00775-014-1214-6 |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Theiner |D Sarah |u Institute of Inorganic Chemistry, University of Vienna, Waehringer Strasse 42, 1090, Vienna, Austria |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Varbanov |D Hristo |u Institute of Inorganic Chemistry, University of Vienna, Waehringer Strasse 42, 1090, Vienna, Austria |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Galanski |D Markus |u Institute of Inorganic Chemistry, University of Vienna, Waehringer Strasse 42, 1090, Vienna, Austria |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Egger |D Alexander |u ADSI-Austrian Drug Screening Institute GmbH, Innrain 66a, 6020, Innsbruck, Austria |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Berger |D Walter |u Research Platform ‘Translational Cancer Therapy Research', University of Vienna, Waehringer Strasse 42, 1090, Vienna, Austria |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Heffeter |D Petra |u Research Platform ‘Translational Cancer Therapy Research', University of Vienna, Waehringer Strasse 42, 1090, Vienna, Austria |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Keppler |D Bernhard |u Institute of Inorganic Chemistry, University of Vienna, Waehringer Strasse 42, 1090, Vienna, Austria |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t JBIC Journal of Biological Inorganic Chemistry |d Springer Berlin Heidelberg |g 20/1(2015-01-01), 89-99 |x 0949-8257 |q 20:1<89 |1 2015 |2 20 |o 775 | ||