A new class of CYP1B1 inhibitors derived from bentranil

作者全名："Yi, Lan; Huang, Xinyue; Yang, Meixian; Cai, Jiajing; Jia, Jianhua; Peng, Zhiping; Zhao, Zhenghuan; Yang, Fengyuan; Qiu, Dachuan"

作者地址："[Yi, Lan; Yang, Meixian; Cai, Jiajing; Jia, Jianhua; Peng, Zhiping; Zhao, Zhenghuan; Qiu, Dachuan] Chongqing Med Univ, Coll Basic Med Sci, Dept Radiat Med, Chongqing 400016, Peoples R China; [Yang, Fengyuan] Chongqing Univ, Sch Pharmaceut Sci, Chongqing 400044, Peoples R China; [Yang, Fengyuan] Chongqing Univ, Innovat Drug Res Ctr, Chongqing 400044, Peoples R China; [Huang, Xinyue] Chongqing Univ Technol, Coll Chem & Chem Engn, Chongqing 400054, Peoples R China"

通信作者："Qiu, DC (通讯作者)，Chongqing Med Univ, Coll Basic Med Sci, Dept Radiat Med, Chongqing 400016, Peoples R China.; Yang, FY (通讯作者)，Chongqing Univ, Sch Pharmaceut Sci, Chongqing 400044, Peoples R China.; Yang, FY (通讯作者)，Chongqing Univ, Innovat Drug Res Ctr, Chongqing 400044, Peoples R China."

来源：BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

ESI学科分类：CHEMISTRY

WOS号：WOS:000917275300001

JCR分区：Q2

影响因子：2.7

年份：2023

卷号：80

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Bentranil; Selectivity; IC50

摘要："Cytochrome P450 1B1 (CYP1B1) is highly expressed in a variety of tumors and implicated to drug resistance. More and more researches have suggested that CYP1B1 is a new target for cancer prevention and therapy. Various CYP1B1 inhibitors with a rigid polycyclic skeleton have been developed, such as flavonoids, trans-stil-benes, and quinazolines. To obtain a new class of CYP1B1 inhibitors, we designed and synthesized a series of bentranil analogues, moreover, IC50 determinations were performed for CYP1B1 inhibition of five of these compounds and found that 6o and 6q were the best inhibitors, with IC50 values in the nM range. The selectivity index (SI) of CYP1B1 over CYP1A1 and CYP1A2 was 30-fold higher than that of alpha-naphthoflavone (ANF). The molecular docking results showed that compound 6q fitted better into the CYP1B1 binding site than other compounds, which was consistent with our experimental results. On the basis of 6o and 6q, it is expected to develop CYP1B1 inhibitors with stronger affinity, higher selectivity and better solubility."

基金机构："National Natural Science Foundation of China [82001869, 51904053]; Chongqing High-level Personnel of Special Support Program (Youth Top-notch Talent) [CQYC201905077]; Creative Research Group of CQ University [CXQT21017]; Science and Technology Research Program of Chongqing Municipal Education Commission [KJQN202200446, KJQN202101142]; Chongqing Science and Technology Bureau [cstc2021jcyj-msxmX0539]"

基金资助正文："The authors gratefully acknowledge research support of this work by National Natural Science Foundation of China (82001869, 51904053), Chongqing High-level Personnel of Special Support Program (Youth Top-notch Talent CQYC201905077), Creative Research Group of CQ University (CXQT21017), the Science and Technology Research Program of Chongqing Municipal Education Commission (KJQN202200446, KJQN202101142), and Chongqing Science and Technology Bureau (cstc2021jcyj-msxmX0539)."