2. Academic Validation
  3. Synthesis, biological evaluation and molecular docking of 4-Amino-2H-benzo[h]chromen-2-one (ABO) analogs containing the piperazine moiety

Synthesis, biological evaluation and molecular docking of 4-Amino-2H-benzo[h]chromen-2-one (ABO) analogs containing the piperazine moiety

  • Bioorg Med Chem. 2019 Oct 15;27(20):115081. doi: 10.1016/j.bmc.2019.115081.
Hong Chen 1,  Jingxiao Zhang 1,  Peixin Hu 1,  Yuna Qian 2,  Jing Li 3,  Jianliang Shen 4
Affiliations

Affiliations

  • 1 Luoyang Key Laboratory of Organic Functional Molecules, College of Food and Drug, Luoyang Normal University, Luoyang 471934, China.
  • 2 State Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325035, China; Wenzhou Institute of Biomaterials and Engineering, Chinese Academy of Science, Wenzhou 325001, China.
  • 3 School of Marine Sciences, Sun Yat-Sen University, Guangzhou 510006, China. Electronic address: lijing356@mail.edu.an.
  • 4 State Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325035, China; Wenzhou Institute of Biomaterials and Engineering, Chinese Academy of Science, Wenzhou 325001, China. Electronic address: shenjl@wibe.ac.cn.
PMID: 31493989 DOI: 10.1016/j.bmc.2019.115081
Abstract

Prostate Cancer (PCa) is a major cause of cancer-related male death in worldwide. To develop of potential anti-prostate Cancer agents, 22 kinds of 4-Amino-2H-benzo[h]chromen-2-one analogs were designed and synthesized as potent Androgen Receptor (AR) antagonist through rational drug modification leading to the discovery of a series of novel antiproliferative compounds. Analogs (3, 4, 5, 7, 8, 10, 11, 12, 16, 18, 21, 23, and 24) exhibited potent antagonistic potency against AR (inhibition >50%), and exhibited potent AR binding affinities as well as displayed the higher activities than finasteride toward LNCaP cells (AR-rich) versus PC-3 cells (AR-deficient). Moreover, the docking study suggested that the most potent antagonist 23 mainly bind to AR ligand binding pocket (LBP) site through Van der Waals' force interactions. The structure-activity relationship (SAR) of these designed 4-Amino-2H-benzo[h]chromen-2-one analogs was rationally explored and discussed. Collectively, this work provides a potential lead compound for Anticancer agent development related to prostate Cancer therapy, and took a step forward towards the development of novel and improved AR antagonists.

Keywords

4-Amino-2H-benzo[h]chromen-2-one analogs; Antagonistic activities; Molecular docking; Prostate cancer; Synthesis.

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