Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, 48, Vas. Constantinou Ave, Athens 11635, Greece.
Eur J Med Chem. 2010 Apr;45(4):1663-6. doi: 10.1016/j.ejmech.2009.12.007. Epub 2010 Jan 13.
Aldose reductase (ALR2) of the polyol metabolic pathway is a target enzyme for the treatment of diabetic complications. A variety of synthetic and natural compounds have been observed to inhibit aldose reductase. Among them, rosmarinic acid has been shown to be in vitro an aldose reductase inhibitor in a micromolar range. In this study, two nitro derivatives of rosmarinic acid synthesized previously, 6'-nitro and 6',6''-dinitrorosmarinic acids, are proposed as aldose reductase inhibitors. Docking studies of the nitro derivatives have been carried out in the active site of aldose reductase. The theoretical results have shown a higher estimated binding energy of both compounds in comparison to that of rosmarinic acid suggesting a higher ALR2 inhibitory activity. The in vitro biological assays confirmed that these compounds were more potent than the parent rosmarinic acid.
醛糖还原酶（ALR2）是多元醇代谢途径的靶酶，可用于治疗糖尿病并发症。已观察到多种合成和天然化合物具有抑制醛糖还原酶的作用。其中，迷迭香酸在体外以微摩尔浓度范围显示为醛糖还原酶抑制剂。在这项研究中，提出了先前合成的迷迭香酸的两种硝基衍生物，6'-硝基和 6'，6''-二硝基迷迭香酸，作为醛糖还原酶抑制剂。已在醛糖还原酶的活性部位进行了硝基衍生物的对接研究。理论结果表明，与迷迭香酸相比，这两种化合物的估计结合能更高，表明它们具有更高的 ALR2 抑制活性。体外生物测定证实，这些化合物比母体迷迭香酸更有效。
