Synthesis, biological evaluation, and molecular docking of novel hydroxyzine derivatives as potential AR antagonists

Yueheng Qi; Baoli Xue; Shijin Chen; Wang Wang; Haifeng Zhou; Hong Chen

doi:10.3389/fchem.2022.1053675

Synthesis, biological evaluation, and molecular docking of novel hydroxyzine derivatives as potential AR antagonists

Front Chem. 2022 Nov 3:10:1053675. doi: 10.3389/fchem.2022.1053675. eCollection 2022.

Authors

Yueheng Qi¹, Baoli Xue^{1

2}, Shijin Chen¹, Wang Wang¹, Haifeng Zhou², Hong Chen¹

Affiliations

¹ Luoyang Key Laboratory of Organic Functional Molecules, College of Food and Drug, Luoyang Normal University, Luoyang, Henan, China.
² Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang, China.

Abstract

Prostate cancer (PCa) is a malignant tumor with a higher mortality rate in the male reproductive system. In this study, the hydroxyazine derivatives were synthesized with different structure from traditional anti-prostate cancer drugs. In the evaluation of in vitro cytotoxicity and antagonistic activity of PC-3, LNCaP, DU145 and androgen receptor, it was found that the mono-substituted derivatives on the phenyl group (4, 6, 7, and 9) displayed strong cytotoxic activities, and compounds 11-16 showed relatively strong antagonistic potency against AR (Inhibition% >55). Docking analysis showed that compounds 11 and 12 mainly bind to AR receptor through hydrogen bonds and hydrophobic bonds, and the structure-activity relationship was discussed based on activity data. These results suggested that these compounds may have instructive implications for drug structural modification in prostate cancer.

Keywords: AR antagonists; antagonistic activity; cytotoxic activity; docking study; hydroxyzine derivatives.