Departments of †Chemistry, ‡Pharmaceutics, and §Chemical Engineering and Materials Science, University of Minnesota , Minneapolis, Minnesota 55455, United States.
J Med Chem. 2014 Mar 27;57(6):2368-79. doi: 10.1021/jm401708f. Epub 2014 Mar 6.
We report here the synthesis and selected properties of various silicate ester derivatives (tetraalkoxysilanes) of the taxanes paclitaxel (PTX) and docetaxel (DTX) [i.e., PTX-OSi(OR)3 and DTX-OSi(OR)3]. Both the hydrophobicity and hydrolytic lability of these silicates can be (independently) controlled by choice of the alkyl group (R). The synthesis, structural characterization, hydrolytic reactivity, and in vitro cytotoxicity against the MDA-MB-231 breast cancer cell line of most of these derivatives are described. We envision that the greater hydrophobicity of these silicates (vis-à-vis PTX or DTX itself) should be advantageous from the perspective of preparation of stable aqueous dispersions of amphiphilic block-copolymer-based nanoparticle formulations.
我们在此报告各种紫杉醇（PTX）和多西他赛（DTX）的硅酸盐酯衍生物（四烷氧基硅烷）的合成和选择性质[即 PTX-OSi（OR）3 和 DTX-OSi（OR）3]。这些硅酸盐的疏水性和水解不稳定性都可以（独立地）通过选择烷基（R）来控制。我们描述了这些衍生物的合成、结构特征、水解反应性以及对 MDA-MB-231 乳腺癌细胞系的体外细胞毒性。我们设想，这些硅酸盐的疏水性（相对于 PTX 或 DTX 本身）对于制备基于两亲性嵌段共聚物的纳米颗粒制剂的稳定水性分散体应该是有利的。
