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

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.

SUBMITTER: Qi Y

PROVIDER: S-EPMC9671208 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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

Qi Yueheng Y Xue Baoli B Chen Shijin S Wang Wang W Zhou Haifeng H Chen Hong H

Frontiers in chemistry 20221103

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 ...[more]

PMID: 36405317

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