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.
