| Literature DB >> 33752554 |
Alexia de Matos Czeczot1,2, Candida Deves Roth1, Rodrigo Gay Ducati1,3, Kenia Pissinate1, Raoní Scheibler Rambo1, Luís Fernando Saraiva Macedo Timmers3, Bruno Lopes Abbadi1, Fernanda Souza Macchi1,2, Víctor Zajaczkowski Pestana1, Luiz Augusto Basso1,2,4, Pablo Machado1,2, Cristiano Valim Bizarro1,2.
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 interactions and ligand conformations. To the best of our knowledge, this study describes the first class of MtFolB inhibitors.Entities:
Keywords: 8-mercaptoguanine; MtDHNA/MtFolB inhibition; Tuberculosis; dihydroneopterin aldolase
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Year: 2021 PMID： 33752554 PMCID： PMC7993393 DOI： 10.1080/14756366.2021.1900157
Source DB: PubMed Journal: J Enzyme Inhib Med Chem ISSN： 1475-6366 Impact factor: 5.051