The androgen receptor (AR) is a steroid hormone receptor and its high expression and disruption of its regulation are strongly implicated in prostate cancer (PCa) development. One of the current therapies includes application of steroidal antiandrogens leading to blockade of the AR action by the abrogation of AR-mediated signaling. We introduced here novel 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused steroidal compounds, described their synthesis based on [8π+2π] cycloaddition reactions of diazafulvenium methides with different steroidal scaffolds and showed their biological evaluation in different prostate cancer cell lines in vitro.

Our results showed the ability of novel compounds to suppress the expression of known androgen receptor targets, Nkx3.1 and PSA in two prostate cell lines, 22Rv1 and VCaP. Candidate compound diminished the transcription of AR-regulated genes in the reporter cell line in a concentration-dependent manner. Antiproliferative activity of the most promising steroid was studied by clonogenic assay and induction of apoptosis in treated cells was documented by immunoblot detection of cleaved PARP.

雄激素受体（AR）是一种类固醇激素受体，其高表达和对其调节的破坏与前列腺癌（PCa）的发展密切相关。当前的疗法之一包括类固醇抗雄激素的应用，其通过消除AR介导的信号传导而导致AR作用的阻断。我们在这里介绍了新颖的4,5,6,7-四氢吡唑并[1,5- a ]吡啶稠合的甾体化合物，描述了它们在[8π+2π]与二氮杂富烯鎓甲基化物与不同甾体骨架的环加成反应的基础上合成的方法，并显示了其生物学评价。在体外不同前列腺癌细胞系中的表达。

我们的结果表明，新型化合物能够抑制两种前列腺细胞系22Rv1和VCaP中已知的雄激素受体靶标Nkx3.1和PSA的表达。候选化合物以浓度依赖的方式减少了报告细胞中AR调节基因的转录。通过克隆形成试验研究了最有前途的类固醇的抗增殖活性，并通过裂解的PARP的免疫印迹检测证明了处理细胞的凋亡诱导作用。