Ethambutol-sugar hybrids as potential inhibitors of mycobacterial cell-wall biosynthesis.
Ethambutol is an established front-line agent for the treatment of tuberculosis, and is also active against Mycobacterium avium infection. However, this agent exhibits toxicity, and is considered to have low potency. The action of ethambutol on the mycobacterial cell wall, particularly the arabinan, and comparison of the structure of ethambutol with several of the cell-wall saccharides, suggested that ethambutol-saccharide hybrids might lead to agents with a more selective mechanism of action. To this end, eight ethambutol-saccharide hybrids were synthesized and screened against M. tuberculosis and several clinical isolates of M. avium.
Reynolds
R C
RC
Southern Research Institute, Birmingham, AL 35205, USA. reynolds@sri.org
Bansal
N
N
Rose
J
J
Friedrich
J
J
Suling
W J
WJ
Maddry
J A
JA
D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002473:Cell Wall / Q000187:drug effects; D004977:Ethambutol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007202:Indicators and Reagents; D009005:Monosaccharides / Q000737:chemistry* / Q000494:pharmacology; D009162:Mycobacterium avium / Q000187:drug effects* / Q000502:physiology; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000502:physiology; D013329:Structure-Activity Relationship
D000995:Antitubercular Agents; D007202:Indicators and Reagents; D009005:Monosaccharides; D004977:Ethambutol