Synthesis and Biological Evaluation of Spirocyclic Chromane Derivatives as a Potential Treatment of Prostate Cancer |
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| Authors: | Li Feng Shujia Yu Hai Wang Shengwei Yang Xue Li Hongjuan Dai Liwen Zhao Cheng Jiang Yazhou Wang |
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| Affiliation: | 1.Department of Medicinal Chemistry, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China;2.Nanjing Sanhome Pharmaceutical Co. Ltd., No. 99, West Yunlianghe Road, Jiangning District, Nanjing 210049, China; (S.Y.); (H.W.); (S.Y.); (X.L.);3.Quality Department, Aurovitas Pharma Taizhou Co. Ltd., Taizhou 225300, China; |
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| 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. |
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| Keywords: | p300/CBP HAT inhibitors antitumor activity |
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