Novel Antiproliferative Chimeric Compounds with Marked Histone Deacetylase Inhibitory Activity
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- 作者：Elisa Giacomini ; Angela Nebbioso ; Alfonso Ciotta ; Cristina Ianni ; Federico Falchi ; Marinella Roberti ; Manlio Tolomeo ; Stefania Grimaudo ; Antonietta Di Cristina ; Rosaria Maria Pipitone ; Lucia Altucci ; Maurizio Recanatini
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2014
- 出版时间：September 11, 2014
- 年：2014
- 卷：5
- 期：9
- 页码：973-978
- 全文大小：329K
- ISSN：1948-5875
文摘
Given our interest in finding potential antitumor agents and in view of the multifactorial mechanistic nature of cancer, in the present work, taking advantage of the multifunctional ligands approach, new chimeric molecules were designed and synthesized by combining in single chemical entities structural features of SAHA, targeting histone deacetylases (HDACs), with substituted stilbene or terphenyl derivatives previously obtained by us and endowed with antiproliferative and pro-apoptotic activity. The new chimeric derivatives were characterized with respect to their cytotoxic activity and their effects on cell cycle progression on different tumor cell lines, as well as their HDACs inhibition. Among the other, trans-6 showed the most interesting biological profile, as it exhibited a strong pro-apoptotic activity in tumor cell lines in comparison with both of its parent compounds and a marked HDAC inhibition.