Schulich Faculty of Chemistry, Technion - Israel Institute of Technology, Haifa, Israel.
Anticancer Agents Med Chem. 2011 May 1;11(4):380-4. doi: 10.2174/187152011795677535.
We report here an investigation that focuses on the organ distribution of metal complexes that are chelated by the amphipolar corrole whose macrocycle is decorated by two sulphonic acid head groups, which are emerging potential therapeutics against cancer (the cytotoxic Ga chelate) and diseases that are characterized by excessive production of ROS and RNS (the cytoprotective Mn and Fe derivatives). We show that the intraperitoneally injected fluorescent gallium(III) derivative accumulates in tissues sections of the kidney, liver, lung, heart, and pancreas. It also reaches the brain blood vessels, but does not cross the blood brain barrier. These findings are of prime importance for future in vivo studies on disease models, as they point toward a large utility of this kind of corrole chelates for treating cancer, neurodegenerative diseases characterized by "leaking BBB", cardiovascular diseases and diabetes.
我们在此报告一项研究,重点关注由两亲性卟啉螯合的金属配合物在器官中的分布,该卟啉大环上装饰有两个磺酸头基,这些配合物是针对癌症(细胞毒性 Ga 螯合物)和以过量产生 ROS 和 RNS 为特征的疾病的潜在治疗药物(细胞保护 Mn 和 Fe 衍生物)。我们表明,腹腔内注射的荧光镓(III)衍生物在肾脏、肝脏、肺、心脏和胰腺的组织切片中积累。它还到达脑血管,但不能穿过血脑屏障。这些发现对未来疾病模型的体内研究至关重要,因为它们表明这种卟啉螯合物在治疗癌症、以“渗漏 BBB”为特征的神经退行性疾病、心血管疾病和糖尿病方面具有广泛的应用。