Design, synthesis and cytotoxicity of novel 3'-N-alkoxycarbonyl docetaxel analogs.
Design, synthesis and cytotoxicity of novel 3'-N-alkoxycarbonyl docetaxel analogs.
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DOI：
10.1016/j.bmcl.2013.10.007
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发表时间：
2013-12
影响因子：
2.7
通讯作者：
Jun Chang;Xiao-dong Hao;Yun Hao;Hong-Fu Lu;Jian-ming Yu;Xun Sun
中科院分区：
文献类型：
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作者：
Jun Chang;Xiao-dong Hao;Yun Hao;Hong-Fu Lu;Jian-ming Yu;Xun Sun
副产物9a对SK-OV-3和A549细胞均有较强的细胞毒作用。通过一维和二维核磁共振实验对9a的结构进行了表征，合成了与9a相同的非对映异构体混合物(16a)和一对非对映异构体(R)-16带(S)-16c。初步的合成孔径雷达研究表明，具有(R)-构型的类似物比具有(S)-构型的类似物稍强一些。此外，α，α-GEM-二甲基类似物16G-I是该系列中最有效的类似物，显示出与多西紫杉醇相似的效力，而比紫杉醇对SK-OV-3细胞株的效力更强。对于A549细胞系，类似物16G-I比多西紫杉醇和紫杉醇都更有效(>；65倍)。
By-product9aexhibited potent cytotoxicity against both SK-OV-3 and A549 cell lines. The structure of9awas characterized using 1D and 2D NMR experiments and confirmed by synthesis to afford a diastereomeric mixture (16a) that was identical to9a, as well as a pair of diastereomers (R)-16band (S)-16c. The preliminary SAR study demonstrated that analogs with an (R)-configuration were slightly more potent than analogs with an (S)-configuration. In addition, α,α-gem-dimethyl analogs16g–iwere the most potent analogs in this series, exhibiting similar potency to docetaxel and greater potency than Taxol against the SK-OV-3 cell line. For the A549 cell line, analogs16g–iwere more potent (>65-fold) than both docetaxel and Taxol.