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.
Somu
Ravindranadh V
RV
Center for Drug Design, Academic Health Center, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Boshoff
Helena
H
Qiao
Chunhua
C
Bennett
Eric M
EM
Barry
Clifton E
CE
Aldrich
Courtney C
CC
D000904:Antibiotics, Antitubercular / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D015195:Drug Design; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017262:Siderophores / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D013329:Structure-Activity Relationship
D000904:Antibiotics, Antitubercular; D009705:Nucleosides; D017262:Siderophores