Ethambutol-sugar hybrids as potential inhibitors of mycobacterial cell-wall biosynthesis

Ethambutol is an established front-line agent for the treatment of tubercul osis, and is also active against Mycobacterium avium infection. However, th is agent exhibits toxicity, and is considered to have low potency. The acti on of ethambutol on the mycobacterial cell wall, particularly the arabinan, and comparison of the structure of ethambutol with several of the cell-wal l saccharides, suggested that ethambutol-saccharide hybrids might lead to a gents with a more selective mechanism of action. To this end, eight ethambu tol-saccharide hybrids were synthesized and screened against M. tuberculosi s and several clinical isolates of M. avium. (C) 1999 Elsevier Science Ltd. All rights reserved.