Spacer optimization of new conjugates for a melanoma-selective delivery approach
In the search for more selective anticancer drugs, we designed and synthesized seven conjugates varying the structure of the linker connecting the 5-iodo-2'-deoxyuridine (IUdR) to the ICF 01012 melanoma-carrier for potential intratumoural specific drug release. Chemical and in vitro metabolic s...
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| Veröffentlicht in: | Organic & biomolecular chemistry 2013-10, Vol.11 (37), p.6372-6384 |
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| container_title | Organic & biomolecular chemistry |
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| creator | André, Mathieu Tarrit, Sébastien Couret, Marie-Joelle Galmier, Marie-Josèphe Débiton, Eric Chezal, Jean-Michel Mounetou, Emmanuelle |
| description | In the search for more selective anticancer drugs, we designed and synthesized seven conjugates varying the structure of the linker connecting the 5-iodo-2'-deoxyuridine (IUdR) to the ICF 01012 melanoma-carrier for potential intratumoural specific drug release. Chemical and in vitro metabolic stability evaluations showed that, except for the ester conjugate (1), the ketal (2b), acetal (2a), carbonate (4) and carbamate (3) conjugates were compatible with our approach. The acetal (2a) and its PEGylated derivative (2c) were of particular interest for further in vivo development owing to their respective pH-dependent stability and limited metabolic degradation in order to exploit the acidic subcellular environment of malignant melanocytes to trigger the release of therapeutics upon internalization in cells. |
| doi_str_mv | 10.1039/c3ob41428k |
| format | Article |
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| ispartof | Organic & biomolecular chemistry, 2013-10, Vol.11 (37), p.6372-6384 |
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| source | MEDLINE; Royal Society Of Chemistry Journals 2008-; Alma/SFX Local Collection |
| subjects | Acetals - chemical synthesis Acetals - chemistry Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - therapeutic use Cells, Cultured Drug Delivery Systems Drug Stability Humans Idoxuridine - analogs & derivatives Idoxuridine - chemical synthesis Idoxuridine - chemistry Melanoma - drug therapy Molecular Structure Quinoxalines - chemistry |
| title | Spacer optimization of new conjugates for a melanoma-selective delivery approach |
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