Design, synthesis and biological evaluation of Pontin ATPase inhibitors through a molecular docking approach
Judith Elkaim1, Marc Lamblin1, Michel Laguerre1
1Université de Bordeaux, CNRS UMR 5248, CBMN, IECB, 2 rue Robert Escarpit, 33607 Pessac, France.
Abstract:
A virtual screening strategy, through molecular docking, for the elaboration of an electronic library of Pontin inhibitors has resulted in the identification of two original scaffolds. The chemical synthesis of four candidates allowed extensive biological evaluations for their anticancer activity. Two compounds displayed an effect on Pontin ATPase activity, and one of them also exhibited a noticeable effect on cell growth. Further biological studies revealed that the most active compound induced apoptotic cell death together with necrosis, this latter effect being likely related to the cellular balance of ATP regulation.
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