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Updated: Sep 23, 2025

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Development of 2-arylbenzo[h]quinolone analogs as selective CYP1B1 inhibitors
Jinyun Dong1, Zengtao Wang1, Qingqing Meng1
1School of Pharmacy, Shanghai Jiao Tong University 800 Dongchuan Road Shanghai China cpucjh@sjtu.edu.cn ssli@sjtu.edu.cn +86 21 34204775 +86 21 34204775.
Abstract:
The CYP1B1 enzyme is regarded as a potential target for cancer prevention and therapy. Based on the structure of α-naphthoflavone (ANF), diverse 2-arylbenzo[h]quinolone derivatives were designed, synthesized and evaluated as selective CYP1B1 inhibitors. Compared with ANF, although few of the title compounds possessed comparable or slightly higher CYP1B1 inhibitory activity, these compounds displayed a significantly increased selectivity toward CYP1B1 over CYP1A2. Among them compounds 5e, 5g and 5h potently inhibited the activity of CYP1B1 with IC50 values of 3.6, 3.9 and 4.1 nM respectively, paralleled by an excellent selectivity profile. On the basis of predicted clog P values, these target compounds may exhibit improved water-solubility compared to ANF. In particular, 5h showed a great superiority in the reversal of CYP1B1-mediated docetaxel resistance in vitro. The current study may serve as a good starting point for the further development of more potent as well as specific CYP1B1 inhibitors capable of reversing CYP1B1-mediated anticancer-drug resistance.
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