Background: For more than 60 years, the lack of new anti-tuberculosis drugs and the
increase of resistant Mycobacterium tuberculosis lineages exhibit a therapeutic challenge, demanding
new options for the treatment of resistant tuberculosis.
Objective: Herein, we determined the (i) activities of (-)-camphene and its derivatives and (ii)
combinatory effect with pyrazinamide (PZA) against Mycobacterium tuberculosis in acidic pH and
(iii) cytotoxicity on VERO cells.
Methods: The activity of (-)-camphene and its 15 derivatives was determined in M. tuberculosis
H37Rv in culture medium at pH 6.0 by Resazurin Microtiter Assay Plate (REMA). The activity and
combinatory study of three (-)-camphene derivatives with PZA was carried out on seven multidrugresistant
(MDR) clinical isolates by REMA and Checkerboard, respectively. The assay of 3-(4,5-
dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) bromide in VERO cells was used to determine
the derivatives’ cytotoxicity.
Results: Four (-)-camphene derivatives, (4), (5a) (5d) and (5h), showed a reduction in the MIC
value at pH 6.0 compared to the MIC detected at pH 6.8 in M. tuberculosis H37
Rv and multidrug
resistant clinical isolates. Three (-)-camphene derivatives, (4), (5d) and (5h), showed synergistic
effect (FICI ≤ 0.5) combined with PZA and were more selective for M. tuberculosis than VERO
cell (selective index from 7.7 to 84.2).
Conclusion: Three (-)-camphene derivatives have shown to be promising anti-TB molecule scaffolds
due to their low MIC values in acidic pH against MDR M. tuberculosis clinical isolates, synergism
with PZA and low cytotoxicity.