Spacer optimization of new conjugates for a melanoma-selective delivery approach

被引：5

作者：

Andre, Mathieu ^{[1
,2
]}

Tarrit, Sebastien ^{[1
,2
]}

Couret, Marie-Joelle ^{[1
,2
]}

Galmier, Marie-Josephe ^{[1
,2
]}

Debiton, Eric ^{[1
,2
]}

Chezal, Jean-Michel ^{[1
,2
]}

Mounetou, Emmanuelle ^{[1
,2
]}

机构：

[1] Univ Auvergne, INSERM, UMR 990, IMTV, F-63005 Clermont Ferrand, France

[2] Univ Auvergne, Clermont Univ, IMTV, F-63005 Clermont Ferrand, France

来源：

ORGANIC & BIOMOLECULAR CHEMISTRY | 2013年 / 11卷 / 37期

关键词：

BIOLOGICAL EVALUATION; PH; DRUGS; THERAPY; DESIGN;

D O I：

10.1039/c3ob41428k

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

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.

引用

收藏

页码：6372 / 6384

页数：13

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