Study on the design, synthesis and structure-activity relationships of new thiosemicarbazone compounds as tyrosinase inhibitors
作者:Senchuan Song、Ao You、Zhiyong Chen、Guoxun Zhu、Huan Wen、Huacan Song、Wei Yi
DOI:10.1016/j.ejmech.2017.08.033
日期:2017.10
of selected compounds 3d and 6e were investigated, revealing that such type of compounds were belonged to the reversible and competitive tyrosinase inhibitors. To verify the safety of these developed thiosemicarbazone compounds, four randomly selected compounds 3d, 4e, 6a and 9a were also tested in 293T cell line for the evaluation of the cytotoxicity. Interestingly, all these compounds almost did not
设计,合成和评估了具有各种取代亲脂性部分(包括取代苯甲醛,取代苯基链烷-1-酮及其联苯型硫代半脲酮类似物)的52种基于结构的硫代半脲化合物,它们是新的酪氨酸酶抑制剂。结果表明22种化合物对酪氨酸酶具有有效的抑制活性,IC 50值低于1.0μM。在获得的实验数据的基础上,合理推导了构效关系。此外,所选化合物3d和6e的抑制机理和抑制动力学进行了研究,发现这类化合物属于可逆和竞争性酪氨酸酶抑制剂。为了验证这些已开发的硫半脲类化合物的安全性,还在293T细胞系中测试了4种随机选择的化合物3d,4e,6a和9a,以评估细胞毒性。有趣的是,所有这些化合物即使在1000μmol/ L的高浓度下也几乎不对293T细胞产生任何毒性。综上所述,这些结果表明此类化合物可以作为治疗酪氨酸酶相关疾病的高效,更安全的候选药物。