Department of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 4 Jagiellońska Str., 41-200 Sosnowiec, Poland.
Int J Mol Sci. 2024 Oct 18;25(20):11211. doi: 10.3390/ijms252011211.
After heart disease, cancer is the second-leading cause of death worldwide. The most effective method of cancer treatment is target therapy. One of the potential goals of therapy could be DT-diaphorase, which reduces quinone moiety to hydroquinone, and reactive oxygen species are create as a byproduct. The obtaining of hybrid compounds containing the quinone moiety and other bioactive compounds leads to new derivatives which can activate DT-diaphorase. The aim of this research was the synthesis and characterization of new hybrids of 5,8-quinolinedione with thymidine derivatives. The analysis of the physicochemical properties shows a strong relationship between the structure and properties of the tested compounds. The enzymatic assay shows that hybrids are good substrates of NQO1 protein. The analysis of the structure-activity relationship shows that the localization of nitrogen atoms influences the enzymatic conversion rate. The analysis was supplemented by a molecular docking study. Comparing the results of the enzymatic assay and the molecular docking presents a strong correlation between the enzymatic conversion rate and the scoring value.
心脏病之后，癌症是全球范围内的第二大死亡原因。癌症治疗最有效的方法是靶向治疗。治疗的潜在目标之一可能是 DT-二氢脱氢酶，它将醌部分还原为对苯二酚，并产生作为副产物的活性氧。获得含有醌部分和其他生物活性化合物的杂合化合物导致可以激活 DT-二氢脱氢酶的新衍生物。本研究的目的是合成和表征与胸苷衍生物的新型 5,8-喹啉二酮杂合物。理化性质分析表明，测试化合物的结构和性质之间存在很强的关系。酶测定表明，杂合物是 NQO1 蛋白的良好底物。结构-活性关系分析表明，氮原子的定位影响酶转化率。分析通过分子对接研究得到补充。比较酶测定结果和分子对接结果表明，酶转化率与评分值之间存在很强的相关性。
