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Discovery of a new class of triazole based inhibitors of acetyl transferase KAT2A.

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.

SUBMITTER: Pacifico R

PROVIDER: S-EPMC9331200 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Discovery of a new class of triazole based inhibitors of acetyl transferase KAT2A.

Pacifico Roberta R Del Gaudio Nunzio N Bove Guglielmo G Altucci Lucia L Siragusa Lydia L Cruciani Gabriele G Ruvo Menotti M Bellavita Rosa R Grieco Paolo P Adamo Mauro F A MFA

Journal of enzyme inhibition and medicinal chemistry 20221201 1

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 affinit ...[more]

PMID: 35880250

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