Novel Isoniazid-Carborane Hybrids Active in Vitro Against .

Tuberculosis (TB) is a severe infectious disease with high mortality and morbidity. The emergence of drug-resistant TB has increased the challenge to eliminate this disease. Isoniazid (INH) remains the key and effective component in the therapeutic regimen recommended by World Health Organization (WHO). A series of isoniazid-carborane derivatives containing 1,2-dicarba--dodecaborane, 1,7-dicarba--dodecaborane, 1,12-dicarba--dodecaborane, or 7,8-dicarba--undecaborate anion were synthesized for the first time. The compounds were tested against the () H37Rv strain and its mutant (D) defective in the synthesis of catalase-peroxidase (KatG). '-((7,8-dicarba--undecaboranyl)methylidene)isonicotinohydrazide () showed the highest activity against the wild-type strain. All hybrids could inhibit the growth of the Δ mutant in lower concentrations than INH. '-([(1,12-dicarba--dodecaboran-1yl)ethyl)isonicotinohydrazide () exhibited more than 60-fold increase in activity against D as compared to INH. This compound was also found to be noncytotoxic up to a concentration four times higher than the minimum inhibitory concentration 99% (MIC) value.