Tetrahydropyrazolo[1,5-a]pyridine-fused steroids and their in vitro biological evaluation in prostate cancer.
作者： Radek Jorda , Susana M.M. Lopes , Eva Řezníčková , Haresh Ajani , António V. Pereira
DOI: 10.1016/J.EJMECH.2019.05.064
关键词:
摘要: Abstract The androgen receptor (AR) is a steroid hormone and its high expression disruption of regulation are strongly implicated in prostate cancer (PCa) development. One the current therapies includes application steroidal antiandrogens leading to blockade AR action by abrogation AR-mediated signaling. We introduced here novel 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused compounds, described their synthesis based on [8π+2π] cycloaddition reactions diazafulvenium methides with different scaffolds showed biological evaluation cell lines in vitro. Our results ability compounds suppress known targets, Nkx3.1 PSA two lines, 22Rv1 VCaP. Candidate compound diminished transcription AR-regulated genes reporter line concentration-dependent manner. Antiproliferative activity most promising was studied clonogenic assay induction apoptosis treated cells documented immunoblot detection cleaved PARP.
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