期刊
BIOORGANIC CHEMISTRY
卷 104, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2020.104198
关键词
Barbituric acid; PARP1 inhibitors; Molecular docking; MDA-MB-436
Six series based on barbituric acid 5a-e, 10a-d; thiobarbituric acid 6a-e, 11a-d and 1,3-dimethylbarbituric acid 7a-e, 12a-d were prepared and screened for their in vitro PARP1 inhibition. They revealed promising inhibition at nanomolar level especially compounds 5c, 7b, 7d and 7e (IC50 = 30.51, 41.60, 41.53 and 36.33 nM) with higher potency than olaparib (IC50 = 43.59 nM). Moreover, compounds 5b, 5d, 7a, 12a and 12c exhibited good comparable activity (IC50 = 65.93, 58.90, 66.57, 45.40 and 50.62 nM, respectively). Furthermore, the most active compounds 5c, 7b, 7d, 7e, 12a and 12c against PARP1 in vitro were evaluated in the BRCA1 mutated triple negative breast cancer cell line MDA-MB-436 where 5c and 12c showed higher potency compared to olaparib and result in cell cycle arrest at G2/M phase. 5c and 12c showed apoptotic effects in MDA-MB-436 and potentiated the cytotoxicity of temozolomide in A549 human lung epithelial cancer cell line. Compounds 5c and 12c represent interesting starting points towards PARP1 inhibitors.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据