期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 27, 期 16, 页码 3683-3687出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2017.07.010
关键词
Heterocyclic chalcones; AhR antagonism; CYP1A1; Chemoprevention; CYP1B1; Cisplatin chemo-resistance
资金
- UK Higher Education Innovation Fund (HEIF)
- Research Business Innovation (RBI) directorate of De Montfort University
- CSIR [BSC-0205]
- CSIR
Inhibitors of CYP1 enzymes may play vital roles in the prevention of cancer and overcoming chemo-resistance to anticancer drugs. In this letter, we report synthesis of twenty-three pyrrole based heterocyclic chalcones which were screened for inhibition of CYP1 isoforms. Compound 3n potently inhibited CYP1B1 with an IC50 of similar to 0.2 mu M in Sacchrosomesm (TM) and CYP1B1-expressing live human cells. However, compound 3j which inhibited both CYP1A1 and CYP1B1 with an IC50 of similar to 0.9 mu M, using the same systems, also potently antagonized B[a]P-mediated induction of AhR signaling in yeast (IC50, 1.5 mu M), fully protected human cells from B[a]P toxicity and completely reversed cisplatin resistance in human cells that overexpress CYP1B1 by restoring cisplatin's cytotoxicity. Molecular modeling studies were performed to rationalize the observed potency and selectivity of enzyme inhibition by compounds 3j and 3n. (C) 2017 Elsevier Ltd. All rights reserved.
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