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.
Keywords: Mycobacterium tuberculosis; acetylcysteine; drug combinations; naphthoquinones; scanning electron microscopy.