Department of Infectious Diseases and Immunology, Indian Institute of Chemical Biology, Jadavpur, Kolkata, West Bengal, India.
Bioorg Med Chem Lett. 2011 Jun 15;21(12):3563-7. doi: 10.1016/j.bmcl.2011.04.127. Epub 2011 May 3.
Heme is an important prosthetic molecule for various hemoproteins and serves important function in living aerobic organisms. But degradation of hemoprotein, for example, hemoglobin during different pathological conditions leads to the release of heme, which is very toxic as it induces oxidative stress and inflammation due to its pro-oxidant nature. Thus, synthesis of compound that will detoxify free heme by interacting with it would be fruitful for the management of heme-induced pathogenesis. Here, we report the synthesis of a novel natural product arborinine and some other acridone derivatives, which interact with free heme. These acridones in vitro block heme-mediated protein oxidation and degradation, markers for heme-induced oxidative stress.
血红素是各种血红素蛋白的重要辅基分子,在需氧生物中起着重要的作用。但在不同的病理条件下,如血红蛋白的降解会导致血红素的释放,由于其具有促氧化剂的性质,血红素会引起氧化应激和炎症,因此非常有毒。因此,合成能与血红素相互作用解毒游离血红素的化合物将有益于血红素诱导的发病机制的管理。在这里,我们报告了一种新型天然产物 Arborinine 和一些其他吖啶酮衍生物的合成,它们与游离血红素相互作用。这些吖啶酮在体外阻止血红素介导的蛋白质氧化和降解,这是血红素诱导的氧化应激的标志物。