Synthesis of Carborane-Containing Flavone and Flavonol Analogues as ER Agonists and COX Inhibitors

  • J Nat Prod. 2026 Apr 24;89(4):1189-1197. doi: 10.1021/acs.jnatprod.5c01639.
Yirong Zhang  1 ,  Chenyang Ma  1 ,  Lili Wang  2 ,  Yuan Li  1  3 ,  Yuzhe Lin  1 ,  Zekun Yang  1 ,  Changxian Yuan  1 ,  Guanxiang Hao  1 ,  Linyuan Wang  1 ,  Hongjing Li  1 ,  Nan Sun  1 ,  Zhangxiang Yin  1 ,  Yong Nian  2 ,  Sinan Wang  1
Affiliations
  • 1. School of Biomedical Engineering & State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University, Shanghai 201210, China.
  • 2. School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • 3. Shanghai Clinical Research and Trial Center, Shanghai 201210, China.
PMID: 41973948 DOI: 10.1021/acs.jnatprod.5c01639
Abstract

Flavones and Flavonols are natural products and privileged structures with diverse bioactivities. Carboranes are considered a three-dimensional bioisosteric surrogate for phenyl rings. Herein, the terminal phenyl group of Flavones and Flavonols was replaced with carborane, and a series of carborane-containing flavone and flavonol analogues were successfully prepared. These compounds exhibited Estrogen Receptor (ER) agonist activities. Compound 1 showed an EC50 of 0.87 ± 0.07 μM for ERα and a selectivity of 12.8-fold toward ERβ. These compounds also showed moderate inhibitory activities toward COX-1 and COX-2.

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