Design, Synthesis, Characterization, and Cytotoxicity of New Pyrazolylmethylene-2-thioxoimidazolidin-4-one Derivatives towards Androgen-Sensitive LNCaP Prostate Cancer Cells

Abstract

A new class of pyrazolylmethylene-2-thioxoimidazolidin-4-one derivatives <b>3a-p</b> were rationally designed and synthesized with the aim of exploring their potential as treatments for prostate cancer. The synthesized compounds <b>3a-p</b> were biologically analyzed for their anticancer effects against AR⁺LNCaP, AR^-PC-3, and Wi38 cell lines. The observed IC₅₀ values against AR⁺LNCaP ranged between 10.27 ± 0.14 and 109.72 ± 2.06 µM after 24 h of incubation. Compounds <b>3i-k</b>, <b>3m</b>, and <b>3o-p</b> recorded IC₅₀ values of 05.22 ± 0.12 to 11.75 ± 0.07 µM after 48 h incubation in the presence of 1 nM DHT, with higher selectivity towards AR⁺LNCaP. Moreover, compounds <b>3i</b> and <b>3k</b> significantly induced Caspase 3 accumulation, reduced DNA content at the various stages of the cell cycle, and ultimately caused AR⁺LNCaP cell growth arrest, as confirmed by cell apoptosis assays. These findings suggest that these analogues of androgen receptor blockers have promising potential for further investigation as effective treatments for prostate cancer.