Mefloquine-inspired quinolines show anti-MAC activity and combine additively with standard drugs
- Treatment of Mycobacterium avium complex lung infections is limited by intrinsic and acquired resistance, prompting a search for new agents.
- A series of amino-alcohol quinolines was designed as mefloquine analogs; structure-activity and cytotoxicity data pointed to the trifluoromethyl and piperazine groups as important.
- One enantiomer, (R)-4c, had the best selectivity and showed additive effects in pairwise combinations with clarithromycin, rifampicin and ethambutol in vitro.
💡 Points
Re-engineering mefloquine's amino-alcohol quinoline is a sensible start, but a lipophilic CF3 plus a basic piperazine is exactly the profile that drives membrane-active, cationic-amphiphilic cytotoxicity, so I'd discount any potency gain until the selectivity window is clear. The (R)-4c enantiomer preference hints at a real target interaction, yet additive rather than synergistic combinations are a thin case for adding it to a regimen.