Synthesis, biological evaluation and molecular docking of 4-Amino-2H-benzo[h]chromen-2-one (ABO) analogs containing the piperazine moiety. Issue 20 (15th October 2019) - Chen, Hong
Graphical abstract: Highlights: A novel of Amino-2H-benzo[ h ]chromen-2-one analogs was synthesized. Antiproliferative and AR antagonist activity of Amino-2H-benzo[ h ]chromen-2-one analogs were investigated. Some Amino-2H-benzo[ h ]chromen-2-one analogs exhibited strong biological activities against AR and LNCaP cells. Molecular docking and SAR of Amino-2H-benzo[ h ]chromen-2-one analogs were also studied. 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, and24 ) 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 antagonist23 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.