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

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 spirocycli...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2021-05, Vol.26 (11), p.3162
Main Authors: Feng, Li, Yu, Shujia, Wang, Hai, Yang, Shengwei, Li, Xue, Dai, Hongjuan, Zhao, Liwen, Jiang, Cheng, Wang, Yazhou
Format: Article
Language:English
Subjects:
antitumor activity
Biological activity
Cell cycle
Cell differentiation
Cell growth
Cell proliferation
Compound A
Design
Epigenetics
Gene expression
Growth inhibition
HAT inhibitors
Hydrocarbons
Hydrogen bonds
Lead compounds
Molecular dynamics
p300/CBP
Pharmacokinetics
Prostate cancer
Proteins
Simulation
Therapeutic applications
Xenografts
Xenotransplantation
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Summary: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 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.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules26113162