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| Content Provider | Springer Nature Link |
|---|---|
| Author | Stíbal, David Therrien, Bru Süss Fink, Georg wak Sliwinska, Patrycja Dyson, Paul J. Čermáková, Eva Řezáčová, Martina Tomšík, Pavel |
| Copyright Year | 2016 |
| Abstract | Four diruthenium trithiolato chlorambucil conjugates have been prepared via Steglich esterification from chlorambucil and the corresponding trithiolato precursors. All conjugates are highly cytotoxic towards human ovarian A2780 and A2780cisR cancer cell lines with IC50 values in the nanomolar range. The conjugates exhibit selectivity towards A2780 cells as compared to non-cancerous HEK293 cells, while being only slightly selective for RF24 and A2780cisR cells. In vivo, the conjugate [10]BF4 suppressed the growth of a solid Ehrlich tumor in immunocompetent NMRI mice but did not prolong their overall survival. The reactivity of the chlorambucil conjugates with glutathione, a potential target of the dinuclear ruthenium motive, and with the 2-deoxyguanosine 5′-monophosphate (dGMP—a model target of chlorambucil) was studied by mass spectrometry and NMR spectroscopy. The conjugates did not show catalytic activity for the oxidation of glutathione nor binding to nucleotides, indicating that glutathione oxidation and DNA alkylation are not key mechanisms of action.Four highly cytotoxic diruthenium trithiolato chlorambucil conjugates have been prepared. All conjugates exhibit selectivity towards A2780 cells as compared to HEK293 cells, while being only slightly active in RF24 and A2780cisR cells. In vivo, the best candidate suppressed the growth of a solid Ehrlich tumor in immunocompetent NMRI mice but did not prolong their overall survival. |
| Starting Page | 443 |
| Ending Page | 452 |
| Page Count | 10 |
| File Format | |
| ISSN | 09498257 |
| Journal | JBIC Journal of Biological Inorganic Chemistry |
| Volume Number | 21 |
| Issue Number | 4 |
| e-ISSN | 14321327 |
| Language | English |
| Publisher | Springer Berlin Heidelberg |
| Publisher Date | 2016-04-04 |
| Publisher Place | Berlin, Heidelberg |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Arene ruthenium Chlorambucil Dinuclear complexes Anticancer activity In vivo study Biochemistry Microbiology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biochemistry Inorganic Chemistry |
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