Synthesis and Biological Evaluation of Spirocyclic Chromane Derivatives as a Potential Treatment of Prostate Cancer

Li Feng, Shujia Yu, Hai Wang, Shengwei Yang, Xue Li, Hongjuan Dai, Liwen Zhao, Cheng Jiang, Yazhou Wang
2021 Molecules  
As a significant co-activator involved in cell cycle and cell growth, differentiation and development, p300/CBP has shown extraordinary potential target in cancer therapy. Herein we designed new compounds from the lead compound A-485 based on molecular dynamic simulations. A series of new spirocyclic chroman derivatives was prepared, characterized and proven to be a potential treatment of prostate cancer. The most potent compound B16 inhibited the proliferation of enzalutamide-resistant 22Rv1
more » ... e-resistant 22Rv1 cells with an IC50 value of 96 nM. Furthermore, compounds B16–P2 displayed favorable overall pharmacokinetic profiles, and better tumor growth inhibition than A-485 in an in vivo xenograft model.
doi:10.3390/molecules26113162 pmid:34070610 fatcat:lzz2al4hrreirdqwrol2fbyi6a