Pyrrolidine-containing or Piperazine-containing Nitrofuranylamides: Design, Synthesis, and In Vitro Anti-mycobacterial Activities

We report herein the design, synthesis, and in vitro anti-mycobacterial activities of 11 pyrrolidine-containing or piperazine-containing nitrofuranylamides. Results revealed that all derivatives 3a-k endowed with excellent activity [minimum inhibitory concentration (MIC): Mycobacterium tuberculosis (MTB) H37Rv strain and more than half of them were more potent than the first-line anti-tuberculosis agents isoniazid (MIC: 0.078 mu g/mL) and rifampicin (MIC: 0.078 mu g/mL). The most active six derivatives were further evaluated against two clinically isolated multidrug-resistant MTB strains resistant to both of isoniazid and rifampicin. In particular, four of them 3a, 3c, 3d, and 3j (MIC: 1.412-3.230 mu g/mL) showed promising activity against the two clinically isolated multidrug-resistant MTB strains and could act as starting points for further investigation.