Design, Synthesis and Anti-Tumor Evaluation of Novel Thiohydantoin Congeners as Androgen Receptor Antagonists With In Vivo Study

Novel thiohydantoin derivatives were designed and synthesized as androgen receptor antagonists, with twelve derivatives fully characterized. The derivative 3a showed the best inhibition of LNCaP cells with an IC50 of 2.64 µM, reducing DNA transactivation of androgens and initiating apoptosis. In vivo, 3a significantly reduced testosterone-induced prostate index and weight, outperforming finasteride, and histopathological examinations confirmed reduced prostate tissue changes and androgen receptor up-regulation. Molecular docking supported the observed biological activity.