Poly(ADP-ribose)polymerase-I (PARP-1) enzyme is involved in maintaining DNA integrity and programmed cell death. A virtual screening of commercial libraries led to the identification of five novel scaffolds with inhibitory profile in the low nanomolar range. A hit-to-lead optimization led to the identification of a group of new potent PARP-1 inhibitors, acyl- piperazinylamides of 3-(4-oxo-3,4-dihydro-quinazolin-2-yl)-propionic acid. Molecular modeling studies highlighted the preponderant role of the propanoyl side chain.
Novel PARP-1 inhibitors based on a 2-propanoyl-3H-quinazolin-4-one scaffold / G. Giannini, G. Battistuzzi, L. Vesci, F.M. Milazzo, F. De Polis, M. Barbarino, M.B. Guglielmi, V. Crollo, G. Gallo, R. Artali, S. Dallavalle. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - 24:2(2014), pp. 462-466. [10.1016/j.bmcl.2013.12.048]
Novel PARP-1 inhibitors based on a 2-propanoyl-3H-quinazolin-4-one scaffold
S. DallavallePenultimo
2014
Abstract
Poly(ADP-ribose)polymerase-I (PARP-1) enzyme is involved in maintaining DNA integrity and programmed cell death. A virtual screening of commercial libraries led to the identification of five novel scaffolds with inhibitory profile in the low nanomolar range. A hit-to-lead optimization led to the identification of a group of new potent PARP-1 inhibitors, acyl- piperazinylamides of 3-(4-oxo-3,4-dihydro-quinazolin-2-yl)-propionic acid. Molecular modeling studies highlighted the preponderant role of the propanoyl side chain.
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