title: Design, synthesis, and biological evaluation of beta-ketosulfonamide adenylation inhibitors as potential antitubercular agents.
abstract: [reaction: see text] The antitubercular nucleoside antibiotics 1 and 2 were recently described that inhibit the adenylate-forming enzyme MbtA and disrupt biosynthesis of the virulence-conferring siderophore known as mycobactin in Mycobacterium tuberculosis. Herein, we report efforts to refine this inhibitor scaffold by replacing the labile acylsulfamate linkage (highlighted) with the more chemically robust beta-ketosulfonamide linkage of 3 and 4.
authors.affiliation: Center for Drug Design, Academic Health Center, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Jagadeshwar
authors.initials: J
authors.lastname: Vannada
authors.forename: Eric M
authors.initials: EM
authors.lastname: Bennett
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wilson
authors.forename: Helena I
authors.initials: HI
authors.lastname: Boshoff
authors.forename: Clifton E
authors.initials: CE
authors.lastname: Barry
authors.forename: Courtney C
authors.initials: CC
authors.lastname: Aldrich
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000995:Antitubercular Agents; D013449:Sulfonamides; D000241:Adenosine