Lapachol was chemically modified to obtain its
thiosemicarbazone and
semicarbazone derivatives. These compounds were tested for antimicrobial activity against several
bacteria and
fungi by the broth microdilution
method. The
thiosemicarbazone and
semicarbazone derivatives of lapachol exhibited antimicrobial activity against the
bacteria Enterococcus faecalis and
Staphylococcus aureus with minimal inhibitory concentrations (MICs) of 0.05 and 0.10 µmol/mL, respectively. The
thiosemicarbazone and
semicarbazone derivatives were also active against the pathogenic
yeast Cryptococcus gattii (MICs of 0.10 and 0.20 µmol/mL, respectively). In addition, the lapachol
thiosemicarbazone derivative was active against 11 clinical isolates of
Paracoccidioides brasiliensis, with MICs ranging from 0.01-0.10 µmol/mL. The lapachol-derived
thiosemicarbazone was not cytotoxic to normal
cells at the concentrations that were active against
fungi and
bacteria. We synthesised, for the first
time,
thiosemicarbazone and
semicarbazone derivatives of lapachol. The MICs for the lapachol-derived
thiosemicarbazone against S. aureus, E. faecalis, C. gattii and several isolates of P. brasiliensis indicated that this compound has the potential to be developed into novel
drugs to treat
infections caused these microbes.