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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Identification of P218 as a potent inhibitor of Mycobacterium ulcerans DHFR

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Author(s):
Riboldi, Gustavo P. [1, 2] ; Zigweid, Rachael [3] ; Myler, Peter J. [3, 4] ; Mayclin, Stephen J. [5, 6] ; Counago, Rafael M. [1, 2] ; Staker, Bart L. [3]
Total Authors: 6
Affiliation:
[1] Univ Estadual Campinas, Dept Genet & Evolucao, Inst Biol, Struct Genom Consortium, BR-13083886 Campinas, SP - Brazil
[2] Univ Estadual Campinas, UNICAMP, Ctr Biol Mol & Engn Genet CBMEG, Ctr Quim Med CQMED, BR-13083875 Campinas, SP - Brazil
[3] Seattle Childrens Res Inst, Ctr Infect Dis Res, Seattle, WA 98109 - USA
[4] Univ Washington, Dept Pediat, Seattle, WA 91895 - USA
[5] Seattle Struct Genom Ctr Infect Dis SSGCID, Seattle, WA 98109 - USA
[6] UCB, Bainbridge Isl, WA 98110 - USA
Total Affiliations: 6
Document type: Journal article
Source: RSC MEDICINAL CHEMISTRY; v. 12, n. 1, p. 103-109, JAN 1 2021.
Web of Science Citations: 0
Abstract

Mycobacterium ulcerans is the causative agent of Buruli ulcer, a debilitating chronic disease that mainly affects the skin. Current treatments for Buruli ulcer are efficacious, but rely on the use of antibiotics with severe side effects. The enzyme dihydrofolate reductase (DHFR) plays a critical role in the de novo biosynthesis of folate species and is a validated target for several antimicrobials. Here we describe the biochemical and structural characterization of M. ulcerans DHFR and identified P218, a safe antifolate compound in clinical evaluation for malaria, as a potent inhibitor of this enzyme. We expect our results to advance M. ulcerans DHFR as a target for future structure-based drug discovery campaigns. (AU)

FAPESP's process: 13/50724-5 - Protein Kinase Chemical Biology Center: supporting drug development through open-access research
Grantee:Paulo Arruda
Support Opportunities: Research Grants - Research Partnership for Technological Innovation - PITE
FAPESP's process: 14/50897-0 - INCT 2014: Open-acess Medicinal Chemistry Centre (OpenMedChem)
Grantee:Katlin Brauer Massirer
Support Opportunities: Research Projects - Thematic Grants