Salicylate metal-binding isosteres as fragments for metalloenzyme inhibition.

ABSTRACT: Metalloenzyme inhibitors typically share a common need to possess a metal-binding pharmacophore (MBP) for binding the active site metal ions. However, MBPs can suffer from physicochemical liabilities, impeding the pharmacological properties and drug-likeliness of inhibitors. To circumvent this, problematic features of the MBP can be identified and exchanged with isosteric replacements. Herein, the carboxylic and hydroxyl group of the salicylic acid MBP were replaced and a total of 27 salicylate metal-binding isosteres (MBIs) synthesized. Of these 27 MBIs, at least 12 represent previously unreported compounds, and the metal-binding abilities of >20 of the MBIs have not been previously reported. These salicylate MBIs were examined for their metal-binding features in model complexes, physicoc

SUBMITTER: Jackl MK 

PROVIDER: S-EPMC8849047 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature