1. Discovery of a new class of triazole based inhibitors of acetyl transferase KAT2A.
- Author
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Pacifico, Roberta, Del Gaudio, Nunzio, Bove, Guglielmo, Altucci, Lucia, Siragusa, Lydia, Cruciani, Gabriele, Ruvo, Menotti, Bellavita, Rosa, Grieco, Paolo, and Adamo, Mauro F. A.
- Subjects
TRIAZOLES ,DRUG discovery ,BINDING site assay ,DRUG development ,CARBOXYLATES - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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