Discovery of a new class of triazole based inhibitors of acetyl transferase KAT2A. (31st December 2022)

• Record Type: Journal Article
• Authors: Pacifico, Roberta; Del Gaudio, Nunzio; Bove, Guglielmo; Altucci, Lucia; Siragusa, Lydia; Cruciani, Gabriele; Ruvo, Menotti; Bellavita, Rosa; Grieco, Paolo; Adamo, Mauro F. A.
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 37:Number 1(2022)
• Page Start: 1987
• Page End: 1994
• Publication Date: 2022-12-31
• Subjects: N-pyridine triazoles -- KAT2A inhibitors -- virtual screening -- acetyl transferases -- anti-cancer; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2022.2097447
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: We have recently developed a new synthetic methodology that provided both N -aryl-5-hydroxytriazoles and N -pyridine-4-alkyl triazoles. A selection of these products was carried through virtual screening towards targets that are contemporary and validated for drug discovery and development. This study determined a number of potential structure target dyads of which N -pyridinium-4-carboxylic-5-alkyl triazole displayed the highest score specificity towards KAT2A. Binding affinity tests of abovementioned triazole and related analogs towards KAT2A confirmed the predictions of the in-silico assay. Finally, we have run in vitro inhibition assays of selected triazoles towards KAT2A; the ensemble of binding and inhibition assays delivered pyridyl-triazoles carboxylates as the prototype of a new class of inhibitors of KAT2A.