Dihydrofusarubin and rifampicin combination prevents pulmonary tuberculosis in murine models of tuberculosis

Tuberculosis is the leading cause of death among the infectious diseases owing to the failure of the present to control the epidemics of the disease. Search for new chemical entities remains the desperate need to control this global scourge. Recently dihydrofusarubin has been reported to exhibit antimicrobial potential. The present study was designed to evaluate the anti-mycobacterial activity of dihydrofusarubin and to examine the efficacy of dihydrofusarubin chemotherapy in murine models of pulmonary tuberculosis (TB). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined by broth microdilution method and viable count method respectively. In vitro drug interaction by checker board assay and dynamics of killing by kill curve method. The two-drug combination was also evaluated for in vivo efficacy in murine models of tuberculosis The MIC of dihydrofusarubin was found to be 8 μg/ml against M. tuberculosis and was found to be bactericidal at 4 × MIC. It demonstrated synergistic interactions with rifampicin and additive interactions with isoniazid and ethambutol under in vitro. Dynamics of the compound was found to be both concentration as well as time dependent. Acute single dose toxicity studies in BALB/c mice demonstrated it to be safe for in vivo studies. In vivo studies revealed its better efficacy both alone as well as in combination with rifampicin. Dihydrofusarubin interacts synergistically with rifampicin both under in vitro and in vivo conditions, thus supporting the view that dihydrofusarubin based drug scaffolds could be promising drug candidates for the treatment of pulmonary tuberculosis.