Synthesis of novel paclitaxel prodrugs designed for bioreductive activation in hypoxic tumour tissue
Synthesis of novel paclitaxel prodrugs designed for bioreductive activation in hypoxic tumour tissue
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DOI：
10.1016/s0968-0896(01)00235-8
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发表时间：
2002-01-01
影响因子：
3.5
通讯作者：
Scheeren, HW
中科院分区：
文献类型：
--
作者：
Damen, EWP;Nevalainen, TJ;Scheeren, HW
介绍了第一批潜在的生物还原紫杉醇前药的合成和初步评价。这些前药被设计为通过靶向低氧肿瘤组织进行更具选择性的化疗的潜在候选药物。芳香族硝基和叠氮基被用作生物还原触发剂。紫杉醇的生成发生在还原和随后的1.6-消除或1，8-消除之后。所有前药在缓冲液中都是稳定的，确实在化学还原芳香硝基或叠氮官能团后得到紫杉醇。在需氧细胞毒性试验中，几种前药的细胞毒性降低。这些化合物是进一步生物评价的有趣候选者。(C)2001爱思唯尔科学有限公司。保留所有权利。
The syntheses and preliminary evaluation of the first potential bioreductive paclitaxel prodrugs are described. These prodrugs were designed as potential candidates in more selective chemotherapy by targeting hypoxic tumour tissue. Aromatic nitro and azide groups were used as the bioreductive trigger. Generation of paclitaxel occurs after reduction and subsequent 1.6-elimination or 1,8-elimination. All prodrugs are stable in buffer and indeed give paclitaxel after chemical reduction of the aromatic nitro or azide functionality. In aerobic cytotoxicity assays several prodrugs exhibit diminished cytotoxicity. These compounds are interesting candidates for further biological evaluation. (C) 2001 Elsevier Science Ltd. All rights reserved.