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.