N-alkylated cyclen cobalt(III) complexes of 1-(chloromethyl)-3-(5,6,7-trimethoxyindol-2-ylcarbonyl)-2,3-dihydro-1H-pyrrolo[3,2-f]quinolin-5-ol DNA alkylating agent as hypoxia-activated prodrugs.
N-alkylated cyclen cobalt(III) complexes of 1-(chloromethyl)-3-(5,6,7-trimethoxyindol-2-ylcarbonyl)-2,3-dihydro-1H-pyrrolo[3,2-f]quinolin-5-ol DNA alkylating agent as hypoxia-activated prodrugs.
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DOI：
10.1016/j.bmc.2011.06.076
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发表时间：
2011-08
影响因子：
3.5
通讯作者：
Guo‐Liang Lu;R. J. Stevenson;J. Chang;P. J. Brothers;D. Ware;W. Wilson;W. Denny;M. Tercel
中科院分区：
文献类型：
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作者：
Guo‐Liang Lu;R. J. Stevenson;J. Chang;P. J. Brothers;D. Ware;W. Wilson;W. Denny;M. Tercel
以一系列n取代环素配体为原料，制备了一系列强效DNA小槽烷基化剂1-（氯甲基）-3-（5,6,7-三甲氧基吲哚-2-羰基）-2,3-二氢- 1h -吡咯[3,2-f]喹啉-5-醇（seco-6-azaCBI-TMI）的钴配合物。最终的n取代配合物的形式总电荷在+2到−2之间，并且溶解度的改善有限。它们表现出与未取代环配体的配合物相似的稳定性，并且与未取代配体的150倍相比，游离烷基化物的细胞毒性衰减大但可变（2 - 30倍）。然而，它们的氧/缺氧比（2 - 22倍）与未取代的环状复合物相当(5)。
A series of cobalt complexes of the potent DNA minor groove alkylator 1-(chloromethyl)-3-(5,6,7-trimethoxyindol-2-ylcarbonyl)-2,3-dihydro-1H-pyrrolo[3,2-f]quinolin-5-ol (seco-6-azaCBI-TMI) were prepared from a series of N-substituted cyclen ligands. The final N-substituted complexes carried formal overall charges ranging from +2 to −2 and showed limited improvements in solubility. They showed similar stabilities to that of the complex with the unsubstituted cyclen ligand, and large but variable attenuation of the cytotoxicity of the free alkylator (2–30-fold), compared to 150-fold for the unsubstituted ligand. However, they had oxic/hypoxic ratios (2–22-fold) comparable to that of the unsubstituted cyclen complex (5).