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

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