硫代氨基脲的合成及其对核糖核苷酸还原酶的抑制活性
Synthesis and ribonucleotide reductase inhibitory activity of thiosemicarbazones.
作者信息
Krishnan Kesavan, Prathiba Kumari, Jayaprakash Venkatesan, Basu Arijit, Mishra Nibha, Zhou Bingsen, Hu Shuya, Yen Yun
机构信息
Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi, Jharkhand 835 215, India.
出版信息
Bioorg Med Chem Lett. 2008 Dec 1;18(23):6248-50. doi: 10.1016/j.bmcl.2008.09.097. Epub 2008 Oct 2.
Ribonucleotide reductase (RR) is an important therapeutic target for anticancer drugs. The structure of human RR features a 1:1 complex of two homodimeric subunits, hRRM1 and hRRM2. Prokaryotically expressed and highly purified recombinant human RR subunits, hRRM1 and hRRM2, were used for holoenzyme-based [(3)H]CDP reduction in vitro assay. Ten new thiosemicarbazones (7-16) were synthesized and screened for their RR inhibitory activity. Two thiosemicarbazones derived from p-hydroxy benzaldehyde (9 and 10) were found to be active but less potent than the standard, Hydroxyurea (HU). Guided by the activity of compounds 9 and 10, 11 new thiosemicarbazones (17-27) derived from p-hydroxy benzaldehyde were prepared and screened for their RR inhibitory activity. All the 11 compounds were more potent than HU.
核糖核苷酸还原酶（RR）是抗癌药物的一个重要治疗靶点。人RR的结构具有两个同二聚体亚基hRRM1和hRRM2的1:1复合物。原核表达并高度纯化的重组人RR亚基hRRM1和hRRM2用于基于全酶的[³H]CDP还原体外测定。合成了10种新的硫代半卡巴腙（7 - 16）并筛选其RR抑制活性。发现两种源自对羟基苯甲醛的硫代半卡巴腙（9和10）具有活性，但效力低于标准品羟基脲（HU）。以化合物9和10的活性为指导，制备了11种源自对羟基苯甲醛的新硫代半卡巴腙（17 - 27）并筛选其RR抑制活性。所有这11种化合物的效力均高于HU。
Zotero 插件