Towards Light-Activated Ruthenium-Arene (RAPTA-Type) Prodrug Candidates
Towards Light-Activated Ruthenium-Arene (RAPTA-Type) Prodrug Candidates
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DOI：
10.1002/cbic.201900236
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发表时间：
2019-11-18
期刊：
影响因子：
3.2
通讯作者：
Dyson, Paul J.
中科院分区：
文献类型：
--
作者：
Renfrew, Anna K.;Karges, Johannes;Dyson, Paul J.
癌症是目前世界上最致命的疾病之一。基于该病的高发病率、与当前化疗相关的副作用和耐药性的出现，人们已经做出了相当大的努力来开发具有新作用模式的新型抗癌药物。金属基化合物由于其代谢机制与有机药物有很大的不同而成为特别有吸引力的候选者。在这方面特别感兴趣的是类型为[Ru(ETA(6)-芳烃)(PTA)Cl2](芳烃：对伞花烃、甲苯、苯等；PTA：1，3，5-三氮-7-磷杂金刚烷)的有机金属Ru(II)配合物，其缩写为Rapta。作为化疗的补充，光激活化疗是一种越来越受到重视的技术，用于治疗多种癌症。有鉴于此，我们设计了一种含叠氮配体的光活性Rapta型配合物。二叠氮化物络合物[Ru(eta(6)-对伞花烃)PTA-(N-3)(2)]在水中是惰性的，但在光照下会缓慢释放叠氮配体。因此，研究了该化合物在黑暗和波长为450 nm的光照下对人宫颈癌(HeLa)和非癌视网膜色素上皮(RPE-1)细胞的体外细胞毒作用。虽然在黑暗中发现该络合物的细胞毒性不大，但在光照下观察到毒性增加。
Cancer is currently one of the deadliest diseases worldwide. Based on the high incidence of this disease, the side effects associated with current chemotherapies and the appearance of drug resistance, considerable efforts have been directed towards the development of new anticancer drugs with new modes of action. Metal-based compounds are particularly attractive candidates due to their metabolic mechanisms, which differ substantially from those of organic drugs. Of special interest in this context are organometallic ruthenium(II) complexes of the type [Ru(eta(6)-arene)(pta)Cl-2] (arene: p-cymene, toluene, benzene, etc.; pta: 1,3,5-triaza-7-phosphaadamantane), which are abbreviated to RAPTA. Complementary to chemotherapy, photoactivated chemotherapy is a technique that has received increasing attention towards the development of treatment for numerous kinds of cancer. With this in mind, a photoactive RAPTA-type complex bearing azide ligands has been designed. The diazide complex, [Ru(eta(6)-p-cymene)pta-(N-3)(2)], is inert in water, but slowly releases the azide ligand upon exposure to light. Consequently, the in vitro cytotoxicity of the complex in the dark and upon light exposure at lambda=450 nm in human cervical carcinoma (HeLa) and noncancerous retinal pigment epithelium (RPE-1) cells was investigated. Although the cytotoxicity of the complex was found to be modest in the dark, an increase in toxicity upon light exposure was observed.