Design and synthesis of new alfa-naphthoflavanones as potent and selective CYP1B1 inhibitors

Abstract

Natural Flavanones are abundant in human diet and a few of them exhibited chemopreventive effects against xenobiotic procarcinogens through the inhibition of tumour specific CYP1B1 enzyme. Herein, a series of new alfa-naphthoflavanones were synthesised and evaluated for their enzymatic inhibitory potency and selectivity of CYP1B1 over its isoenzyme CYP1A1. The most active compound 8c displayed highest inhibitory potency against CYP1B1 with the IC₅₀ value of 0.1 nM. The structure activity relationship studies implied that the methoxy groups on the core scaffold of naphthalene ring significantly influenced CYP1B1 inhibition efficacy, while B-ring substitutions played important roles in activity. Molecular docking studies were conducted to provide a better understanding on the key structural features involved in CYP1B1 inhibitory activity. The results of the study implied that these naphthoflavanones could be considered as new leads and further investigation be conducted to explore the flavanone scaffold as skeleton for inhibiting CYP1B1.

Graphic abstract

Keywords:

• Natural flavonoids
• CYP1B1 inhibitors
• naphthoflavanones
• structure activity relationships
• molecular docking

Acknowledgments

We would like to thank Prof. Shaoshun Li in School of Pharmacy, Shanghai Jiaotong University, for his generous help in the biological evaluation.

Disclosure statement

All authors declare that they have no competing interests.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.