Evaluation of amentoflavone metabolites on PARP-1 inhibition and the potentiation on anti-proliferative effects of carboplatin in A549 cells.
Evaluation of amentoflavone metabolites on PARP-1 inhibition and the potentiation on anti-proliferative effects of carboplatin in A549 cells.
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DOI：
10.1016/j.bmcl.2021.128480
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发表时间：
2021-11
影响因子：
2.7
通讯作者：
Bao-Lin Wang;Xiao-long Hu;Rong Wang;L. Huan;Hao Wang
中科院分区：
文献类型：
--
作者：
Bao-Lin Wang;Xiao-long Hu;Rong Wang;L. Huan;Hao Wang
The present study aims to determine the major metabolites of amentoflavone (AMF) and further evaluate their inhibitory effects on PARP-1. First, different fractions (Frs.1–9), which were collected according to retention time ofAMFmetabolites based on UHPLC-QTOF-MS/MS qualitative analysis, were evaluated on their inhibitory effects against PARP-1. Then, two mono-sulfate metabolites in the fractions with potent PARP-1 inhibitory effect were targetedly semi-synthesized. Moreover, three mono-sulfate conjugates (compound8,9and10), including one disulfate conjugate (compound10), were isolated and their structures were fully elucidated by UHPLC-QTOF-MS/MS and NMR. Finally, the binding mode of compound8(amentoflavone-4‴-O-sulfate) toward PARP-1 and its potentiation on carboplatin (CBP) in A549 cells were investigated.This study was the first report on bioactivity evaluation ofAMFmetabolites in rat bile on PARP-1 and the potentiation of compound8on carboplatin (CBP) in A549 cellsin vitro. This paper also provided scientific basis for theAMFmetabolites on PARP-1 inhibition and chemosensitization.
