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

ABSTRACT: 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.

SUBMITTER: Feng L

PROVIDER: S-EPMC8198214 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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

Feng Li L Yu Shujia S Wang Hai H Yang Shengwei S Li Xue X Dai Hongjuan H Zhao Liwen L Jiang Cheng C Wang Yazhou Y

Molecules (Basel, Switzerland) 20210525 11

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 <b>B16</b> inhibited the proliferation of enzalutamide-resistant 2 ...[more]

PMID: 34070610

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