端粒酶
化学
体外
铅化合物
生物化学
组合化学
基因
作者
Maria Menichincheri,Dario Ballinari,Alberto Bargiotti,L. Bonomini,Walter Ceccarelli,Roberto D’Alessio,Antonella Fretta,Jürgen Moll,Paolo Polucci,Chiara Soncini,Marcellino Tibolla,Jean‐Yves Trosset,Ermes Vanotti
摘要
In recent years telomerase has been identified as a new promising target in oncology and consequently new telomerase inhibitors have been intensely explored as anticancer agents. Focused screening of several polyhydroxylated flavonoids has allowed us to identify 7,8,3‘,4‘-tetrahydroxyflavone 1 as a new telomerase inhibitor with an interesting in vitro activity in a Flash-Plate assay (IC50 = 0.2 μM) that has been confirmed in the classical TRAP assay. Starting from this compound, we developed a medicinal chemistry program to optimize our lead, and in particular to replace one of the two catechols with potential bioisosteres. From this study, new structural analogues characterized by submicromolar potencies have been obtained. Their synthesis and biological activity are described.
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