In vitro, in vivo, and intracellular chemotherapeutic activity of B746, a clofazimine analogue against Mycobacterium avium complex

B746, an analogue of clofazimine, was compared with the parent compound for its activity against Mycobacterium avium complex (MAC), using several methods. All the studies using simulated in vivo conditions, and those with macrophages from healthy mice or from those treated with these drugs, revealed B746 to be similar to clofazimine. When used alone against experimental MAC infections in beige mice, B746 required an optimal dose of 20 mg/kg. At that dose it proved to be inferior to clofazimine, given at the same dose, but was slightly superior to streptomycin given intramuscularly at 150 mg/kg. On the other hand, in combination with other drugs, it proved to be inferior when given along with either clofazimine or streptomycin. Addition of B746 did not improve the chemotherapeutic efficacy of streptomycin-clofazimine combination in the treatment of established MAC infections of beige mice.