Antituberculosis Activities of Lapachol and β-Lapachone in Combination with Other Drugs in Acidic pH.

Background

The treatment of multidrug-resistant tuberculosis (MDR-TB) is a challenge to be overcome. The increase of resistant isolates associated with serious side effects during therapy leads to the search for substances that have anti-TB activity, which make treatment less toxic, and also act in the macrophage acidic environment promoted by the infection.

Objective

The aim of this study was to investigate lapachol and β-lapachone activities in combination with other drugs against Mycobacterium tuberculosis at neutral and acidic pH and its cytotoxicity.

Design

Inhibitory and bactericidal activities against M. tuberculosis and clinical isolates were determined. Drug combination and cytotoxicity assay were carried out using standard TB drugs and/or N-acetylcysteine (NAC).

Results

Both naphthoquinones presented activity against MDR clinical isolates. The combinations with the first-line TB drugs demonstrated an additive effect and β-lapachone+NAC were synergic against H37Rv. Lapachol activity at acidic pH and its association with NAC improved the selectivity index. Lapachol and β-lapachone produced cell morphological changes in bacilli at pH 6.0 and 6.8, respectively.

Conclusion

Lapachol revealed promising anti-TB activity, especially associated with NAC.