2. Academic Validation
  3. A new class of CYP1B1 inhibitors derived from bentranil

A new class of CYP1B1 inhibitors derived from bentranil

  • Bioorg Med Chem Lett. 2023 Jan 15;80:129112. doi: 10.1016/j.bmcl.2022.129112.
Lan Yi 1,  Xinyue Huang 2,  Meixian Yang 1,  Jiajing Cai 1,  Jianhua Jia 1,  Zhiping Peng 1,  Zhenghuan Zhao 1,  Fengyuan Yang 3,  Dachuan Qiu 4
Affiliations

Affiliations

  • 1 Department of Radiation Medicine, College of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China.
  • 2 College of Chemistry and Chemical Engineering, Chongqing University of Technology, Chongqing 400054, China.
  • 3 School of Pharmaceutical Sciences and Innovative Drug Research Centre, Chongqing University, Chongqing 400044, China. Electronic address: kristen@cqu.edu.cn.
  • 4 Department of Radiation Medicine, College of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China. Electronic address: 102899@cqmu.edu.cn.
PMID: 36565966 DOI: 10.1016/j.bmcl.2022.129112
Abstract

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-stilbenes, 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 α-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.

Keywords

Bentranil; CYP1B1; CYP1B1 inhibitors; IC(50); Selectivity.

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