化学
IC50型
铅化合物
组合化学
对接(动物)
聚ADP核糖聚合酶
细胞生长
分子
立体化学
体外
生物化学
酶
有机化学
聚合酶
医学
护理部
作者
Hui Shen,Yiran Ge,Junwei Wang,Hui Li,Yungen Xu,Qihua Zhu
标识
DOI:10.1016/j.bmcl.2021.128169
摘要
Two series of novel compounds with inhibition activity against PARP-1 were designed and synthesized. All target compounds were evaluated for their PARP-1 inhibition activity, and compounds with high PARP-1 inhibition activity were selected to assess for cellular assays in vitro. Among them, compound II-4 displayed impressive results in both PARP-1 enzyme inhibition with IC50 value of 0.51 nM and anti-proliferation activity against HCT116 and HCC1937 cell lines with IC50 values of 6.62 nM and 12.65 nM, respectively. Also, II-4 exhibited good metabolic stability in vitro with t1/2 of 173.25 min and CLint of 0.04 mL/min/mg. Prediction of molecular properties and protein docking were applied to structure design. Our study provides potential lead compounds and design directions for the development of PARP-1 inhibitors.
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