publication . Other literature type . Article . 2006

Antitubercular Nucleosides That Inhibit Siderophore Biosynthesis: SAR of the Glycosyl Domain

Ravindranadh V. Somu; Daniel J. Wilson; Eric M. Bennett; Helena I. Boshoff; Laura Celia; Brian J. Beck; Clifton E. Barry; Courtney C. Aldrich;
Open Access English
  • Published: 28 Dec 2006
Abstract
Tuberculosis (TB) is the leading cause of infectious disease mortality in the world by a bacterial pathogen. We previously demonstrated that a bisubstrate inhibitor of the adenylation enzyme MbtA, which is responsible for the second step of mycobactin biosynthesis, exhibited potent antitubercular activity. Here we systematically investigate the structure activity relationships of the bisubstrate inhibitor glycosyl domain resulting in the identification of a carbocyclic analogue that possesses a KIapp value of 2.3 nM and MIC99 values of 1.56 μM against M. tuberculosis H37Rv. The SAR data suggest the intriguing possibility that the bisubstrate inhibitors utilize a...
Subjects
free text keywords: Article, Molecular Medicine, Drug Discovery, Mycobacterium tuberculosis, biology.organism_classification, biology, Biosynthesis, chemistry.chemical_compound, chemistry, Enzyme, chemistry.chemical_classification, Glycosyl, Structure–activity relationship, Stereochemistry, Nucleoside, Mycobactin, Biochemistry, Adenylylation
Abstract
Tuberculosis (TB) is the leading cause of infectious disease mortality in the world by a bacterial pathogen. We previously demonstrated that a bisubstrate inhibitor of the adenylation enzyme MbtA, which is responsible for the second step of mycobactin biosynthesis, exhibited potent antitubercular activity. Here we systematically investigate the structure activity relationships of the bisubstrate inhibitor glycosyl domain resulting in the identification of a carbocyclic analogue that possesses a KIapp value of 2.3 nM and MIC99 values of 1.56 μM against M. tuberculosis H37Rv. The SAR data suggest the intriguing possibility that the bisubstrate inhibitors utilize a...
Subjects
free text keywords: Article, Molecular Medicine, Drug Discovery, Mycobacterium tuberculosis, biology.organism_classification, biology, Biosynthesis, chemistry.chemical_compound, chemistry, Enzyme, chemistry.chemical_classification, Glycosyl, Structure–activity relationship, Stereochemistry, Nucleoside, Mycobactin, Biochemistry, Adenylylation
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publication . Other literature type . Article . 2006

Antitubercular Nucleosides That Inhibit Siderophore Biosynthesis: SAR of the Glycosyl Domain

Ravindranadh V. Somu; Daniel J. Wilson; Eric M. Bennett; Helena I. Boshoff; Laura Celia; Brian J. Beck; Clifton E. Barry; Courtney C. Aldrich;