Rationally Designed Nucleoside Antibiotics That Inhibit Siderophore Biosynthesis of Mycobacterium tuberculosis

A rationally designed nucleoside inhibitor of Mycobacterium tuberculosis growth (MIC(99) = 0.19 microM) that disrupts siderophore biosynthesis was identified. The activity is due to inhibition of the adenylate-forming enzyme MbtA which is involved in biosynthesis of the mycobactins.

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Bibliographische Detailangaben
Veröffentlicht in:	Journal of medicinal chemistry 2006-01, Vol.49 (1), p.31-34
Hauptverfasser:	SOMU, Ravindranadh V., BOSHOFF, Helena, QIAO, Chunhua, BENNETT, Eric M., BARRY, Clifton E., ALDRICH, Courtney C.
Format:	Artikel
Sprache:	eng
Schlagworte:	Antibacterial agents Antibiotics, Antitubercular - chemical synthesis Antibiotics, Antitubercular - chemistry Antibiotics, Antitubercular - pharmacology Antibiotics. Antiinfectious agents. Antiparasitic agents Biological and medical sciences Crystallography, X-Ray Drug Design Medical sciences Microbial Sensitivity Tests Models, Molecular Molecular Structure Mycobacterium tuberculosis - drug effects Nucleosides - chemical synthesis Nucleosides - chemistry Nucleosides - pharmacology Pharmacology. Drug treatments Siderophores - antagonists & inhibitors Siderophores - biosynthesis Structure-Activity Relationship
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Beschreibung
Zusammenfassung:	A rationally designed nucleoside inhibitor of Mycobacterium tuberculosis growth (MIC(99) = 0.19 microM) that disrupts siderophore biosynthesis was identified. The activity is due to inhibition of the adenylate-forming enzyme MbtA which is involved in biosynthesis of the mycobactins.
ISSN:	0022-2623 1520-4804
DOI:	10.1021/jm051060o