Developing Metal-Binding Isosteres of 8-Hydroxyquinoline as Metalloenzyme Inhibitor Scaffolds.

ABSTRACT: The use of metal-binding pharmacophores (MBPs) in fragment-based drug discovery has proven effective for targeted metalloenzyme drug development. However, MBPs can still suffer from pharmacokinetic liabilities. Bioisostere replacement is an effective strategy utilized by medicinal chemists to navigate these issues during the drug development process. The quinoline pharmacophore and its bioisosteres, such as quinazoline, are important building blocks in the design of new therapeutics. More relevant to metalloenzyme inhibition, 8-hydroxyquinoline (8-HQ) and its derivatives can serve as MBPs for metalloenzyme inhibition. In this report, 8-HQ isosteres are designed and the coordination chemistry of the resulting metal-binding isosteres (MBIs) is explored using a bioinorganic model complex. In

SUBMITTER: Seo H 

PROVIDER: S-EPMC9912809 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature