1. Discovery of a Selective Series of Inhibitors of Plasmodium falciparum HDACs
- Author
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Nadia Gennari, Emanuela Nizi, Steven J. Harper, Savina Malancona, Sergio Altamura, Edith Monteagudo, David Roberts, Ilaria Biancofiore, Paul Willis, Maria Vittoria Orsale, Ottavia Cecchetti, Antonella Cellucci, Ralph Laufer, Rita Graziani, Alberto Bresciani, Simona Ponzi, Jesus Maria Ontoria Ontoria, Maria Veneziano, Annalise Di Marco, Giacomo Paonessa, Vincenzo Summa, Federica Ferrigno, Ontoriajm, G Paonessa, G, Ponzi, S, Ferrigno, F, Nizi, E, Biancofiore, I, Malancona, S, Graziani, R, Roberts, D, Willis, P, Bresciani, A, Nadia Gennari, N, Cecchetti, O, Monteagudo, E, Orsale, Mv, Veneziano, M, Di Marco, A, Cellucci, A, Laufer, R, Sergio Altamura, S, Summa, V, and Harper, S
- Subjects
0301 basic medicine ,biology ,Chemistry ,030106 microbiology ,Organic Chemistry ,Growth inhibitory ,Plasmodium falciparum ,biology.organism_classification ,Biochemistry ,03 medical and health sciences ,030104 developmental biology ,Mechanism of action ,Drug Discovery ,medicine ,medicine.symptom - Abstract
The identification of a new series of P. falciparum growth inhibitors is described. Starting from a series of known human class I HDAC inhibitors a SAR exploration based on growth inhibitory activity in parasite and human cells-based assays led to the identification of compounds with submicromolar inhibition of P. falciparum growth (EC50500 nM) and good selectivity over the activity of human HDAC in cells (up to50-fold). Inhibition of parasital HDACs as the mechanism of action of this new class of selective growth inhibitors is supported by hyperacetylation studies.
- Published
- 2015