Metwally Kamel, Pratsinis Harris, Kletsas Dimitris, Quattrini Luca, Coviello Vito, Motta Concettina La, El-Rashedy Ahmed A, Soliman Mahmoud Es
Department of Medicinal Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
Laboratory of Cell Proliferation & Ageing, Institute of Biosciences & Applications, National Centre of Scientific Research 'Demokritos', Athens, Greece.
Future Med Chem. 2017 Dec;9(18):2147-2166. doi: 10.4155/fmc-2017-0149. Epub 2017 Nov 3.
Targeting aldose reductase enzyme with 2,4-thiazolidinedione-3-acetic acid derivatives having a bulky hydrophobic 3-arylquinazolinone residue.
MATERIALS & METHODS: All the target compounds were structurally characterized by different spectroscopic methods and microanalysis, their aldose reductase inhibitory activities were evaluated, and binding modes were studied by molecular modeling.
All the synthesized compounds proved to inhibit the target enzyme potently, exhibiting IC values in the nanomolar/low nanomolar range. Compound 5i (IC = 2.56 nM), the most active of the whole series, turned out to be almost 70-fold more active than the only marketed aldose reductase inhibitor epalrestat.
This work represents a promising matrix for developing new potential therapeutic candidates for prevention of diabetic complications through targeting aldose reductase enzyme. [Formula: see text].
用具有庞大疏水3 - 芳基喹唑啉酮残基的2,4 - 噻唑烷二酮 - 3 - 乙酸衍生物靶向醛糖还原酶。
所有目标化合物通过不同的光谱方法和微量分析进行结构表征，评估其醛糖还原酶抑制活性，并通过分子建模研究结合模式。
所有合成化合物均被证明能有效抑制目标酶，IC值处于纳摩尔/低纳摩尔范围。化合物5i（IC = 2.56 nM）是整个系列中活性最高的，其活性比唯一上市的醛糖还原酶抑制剂依帕司他高出近70倍。
这项工作为通过靶向醛糖还原酶开发预防糖尿病并发症的新潜在治疗候选物提供了一个有前景的基础。[公式：见正文]
