OBJECTIVES: The antimycobacterial activities of RS-112997, RS-124922 and 
RS-118641, three capuramycin analogues that inhibit 
phospho-N-acetylmuramyl-pentapeptide translocase, were tested against clinical 
isolates of Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium 
intracellulare.
METHODS AND RESULTS: MICs were determined by the broth microdilution method 
using a modified Middlebrook 7H9 broth. RS-118641 was the most potent compound 
overall. The MIC50/90 (mg/L) results for RS-118641 were: M. tuberculosis, 1/2; 
multidrug-resistant (MDR) M. tuberculosis, 0.5/2; M. avium, 4/8; and M. 
intracellulare, 0.06/0.5. No statistically significant differences in MIC 
distributions were observed between non-MDR and MDR M. tuberculosis for any of 
the capuramycin analogues tested. In order to evaluate the therapeutic efficacy 
of RS-112997 and RS-124922 in a murine lung model of tuberculosis, both 
compounds were administered intranasally at 0.1 or 1 mg/mouse/day for 12 days. 
The mycobacterial load in the lungs was significantly lower in all treatment 
groups than in the untreated controls. Additional experiments were performed to 
evaluate the therapeutic efficacy of the three compounds against the M. 
intracellulare infection in mice. All compounds were administered intranasally 
at 0.1 mg/mouse/day for 21 days. The mycobacterial load in the lungs was 
significantly lower in all treatment groups than in the untreated controls.
CONCLUSIONS: These results suggest that capuramycin analogues exhibit strong 
antimycobacterial potential and should be considered for further evaluation in 
the treatment of M. tuberculosis and M. avium-M. intracellulare complex 
infections in humans.