| Autor: |
Quattrini L; Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy., Sadiq M; Institute of Cancer Therapeutics, School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, West Yorkshire BD7 1DP, UK., Petrarolo G; Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy., Maitland NJ; Cancer Research Unit, Department of Biology, University of York, Heslington, North Yorkshire YO10 5DD, UK., Frame FM; Cancer Research Unit, Department of Biology, University of York, Heslington, North Yorkshire YO10 5DD, UK., Pors K; Institute of Cancer Therapeutics, School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, West Yorkshire BD7 1DP, UK., La Motta C; Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy.; CISUP, Centre for Instrumentation Sharing, University of Pisa, Lungarno Pacinotti 43, 56128 Pisa, Italy. |
| Abstrakt: |
Prostate cancer represents the most common malignancy diagnosed in men, and is the second-leading cause of cancer death in this population. In spite of dedicated efforts, the current therapies are rarely curative, requiring the development of novel approaches based on innovative molecular targets. In this work, we validated aldehyde dehydrogenase 1A1 and 1A3 isoform expressions in different prostatic tissue-derived cell lines (normal, benign and malignant) and patient-derived primary prostate tumor epithelial cells, demonstrating their potential for therapeutic intervention using a small library of aldehyde dehydrogenase inhibitors. Compound 3b , 6-(4-fluorophenyl)-2-phenylimidazo [1,2- a ]pyridine exhibited not only antiproliferative activity in the nanomolar range against the P4E6 cell line, derived from localized prostate cancer, and PC3 cell lines, derived from prostate cancer bone metastasis, but also inhibitory efficacy against PC3 colony-forming efficiency. Considering its concomitant reduced activity against normal prostate cells, 3b has the potential as a lead compound to treat prostate cancer by means of a still untapped molecular target. |
