8-Mercaptoguanine-based inhibitors of Mycobacterium tuberculosis dihydroneopterin aldolase: synthesis, in vitro inhibition and docking studies.

ABSTRACT: The dihydroneopterin aldolase (DHNA, EC 4.1.2.25) activity of FolB protein is required for the conversion of 7,8-dihydroneopterin (DHNP) to 6-hydroxymethyl-7,8-dihydropterin (HP) and glycolaldehyde (GA) in the folate pathway. FolB protein from Mycobacterium tuberculosis (MtFolB) is essential for bacilli survival and represents an important molecular target for drug development. S8-functionalized 8-mercaptoguanine derivatives were synthesised and evaluated for inhibitory activity against MtFolB. The compounds showed IC₅₀ values in the submicromolar range. The inhibition mode and inhibition constants were determined for compounds that exhibited the strongest inhibition. Additionally, molecular docking analyses were performed to suggest enzyme-inhibitor interac

SUBMITTER: Czeczot AM 

PROVIDER: S-EPMC7993393 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature