Design and Biological Evaluation of Manganese- and Ruthenium-Based Hybrid CO-RMs (HYCOs)
Design and Biological Evaluation of Manganese- and Ruthenium-Based Hybrid CO-RMs (HYCOs)
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DOI：
10.1002/cmdc.201900426
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发表时间：
2019-08-23
期刊：
影响因子：
3.4
通讯作者：
Rivard, Michael
中科院分区：
文献类型：
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作者：
Ollivier, Anthony;Foresti, Roberta;Rivard, Michael
一氧化碳(CO)是血红素加氧酶-1(HO-1)催化血红素降解的产物，对其治疗作用的兴趣导致了CO释放分子(CO-RMS)的开发，以控制体内这种气体的释放。最近，我们建议将调控HO-1表达的转录因子核因子红系相关因子2(Nrf2)的不同激活剂与钴基CO-RM结合，以发挥外源性和内源性CO的有益作用。在这项研究中，我们描述了一种杂化分子(称为HYCOs)的制备，该杂化分子将富马酸衍生物作为NRF2激活剂连接到已知具有药理活性的基于Mn或Ru的CO-RM上。除了酰基-锰络合物外，这些杂化化合物是通过可变结构的连接物将两个生物活性实体结合在一起得到的。文中还进行了X射线衍射分析和初步的生物学研究。
Interest in the therapeutic effects of carbon monoxide (CO), a product of heme degradation catalyzed by the enzyme heme oxygenase-1 (HO-1), has led to the development of CO-releasing molecules (CO-RMs) for the controlled delivery of this gas in vivo. We recently proposed conjugating a cobalt-based CO-RM with various activators of nuclear factor erythroid 2-related factor 2 (Nrf2), the transcription factor that regulates HO-1 expression, in order to exploit the beneficial effects of exogenous and endogenous CO. In this study, we describe the preparation of hybrid molecules (termed HYCOs) conjugating a fumaric acid derivative as an Nrf2 activator to a Mn- or a Ru-based CO-RM known to be pharmacologically active. With the exception of an acyl-manganese complex, these hybrids were obtained by associating the two bioactive entities by means of a linker of variable structure. X-ray diffraction analyses and preliminary biological investigations are also presented.