Novel PARP-1 inhibitors based on a 2-propanoyl-3H-quinazolin-4-one scaffold

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• 作者：Giuseppe Giannini ; Gianfranco Battistuzzi ; Loredana Vesci ; Ferdin ; o M. Milazzo ; Francesca De Paolis ; Marcella Barbarino ; Mario Berardino Guglielmi ; Valeria Carollo ; Grazia Gallo ; Roberto Artali ; Sabrina Dallavalle
• 关键词：PARP-1 inhibitors ; Anticancer ; 3-(4-Oxo-3 ; 4-dihydro-quinazolin-2-yl)-propionamides ; Molecular modeling ; Virtual screening of commercial libraries ; Hit-to-lead optimization
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：15 January, 2014
• 年：2014
• 卷：24
• 期：2
• 页码：462-466
• 全文大小：793 K

文摘

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.