Qi Yueheng, Chen Hong, Chen Shijin, Shen Jianliang, Li Jingguo
Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Luoyang Key Laboratory of Organic Functional Molecules, College of Food and Drug, Luoyang Normal University, Luoyang, Henan, China.
Front Chem. 2022 Aug 15;10:947065. doi: 10.3389/fchem.2022.947065. eCollection 2022.
Prostate cancer is one of the malignant tumors and the second most common malignant tumor in men. Clinically used androgen receptor (AR)-targeted drugs can antagonize androgen and inhibit tumor growth, but these drugs can cause serious resistance problems. To develop novel AR antagonists, 22 kinds of arylpiperazine derivatives were designed and synthesized, and the derivatives , , , , , , , and not only showed strong antagonistic potency (>55% inhibition) and binding affinities (IC <3 μM) to AR, but also showed stronger inhibitory activity to LNCaP cells PC-3 cells. Among them, derivative exhibited the highest binding affinity for AR (IC = 0.65 μM) and the highest antagonistic potency (76.2% inhibition). Docking studies suggested that the derivative is primarily bound to the AR-LBP site by the hydrophobic interactions. Overall, those results provided experimental methods for developing novel arylpiperazine derivatives as potent AR antagonists.
前列腺癌是一种恶性肿瘤，是男性中第二常见的恶性肿瘤。临床上使用的雄激素受体（AR）靶向药物可以拮抗雄激素并抑制肿瘤生长，但这些药物会引发严重的耐药性问题。为了开发新型AR拮抗剂，设计并合成了22种芳基哌嗪衍生物，其中衍生物 、 、 、 、 、 、 和 不仅对AR表现出强大的拮抗效力（抑制率>55%）和结合亲和力（IC<3 μM），而且对LNCaP细胞和PC-3细胞表现出更强的抑制活性。其中，衍生物 对AR表现出最高的结合亲和力（IC = 0.65 μM）和最高的拮抗效力（抑制率76.2%）。对接研究表明，衍生物 主要通过疏水相互作用与AR-LBP位点结合。总体而言，这些结果为开发新型芳基哌嗪衍生物作为有效的AR拮抗剂提供了实验方法。
