The antimicrobial activity of lapachol and its thiosemicarbazone and semicarbazone derivatives

• Published in: Memórias do Instituto Oswaldo Cruz 2014-01, Vol.108 (3)
• Main Authors: Souza, Marina Azevêdo, Johann, Susana, Lima, Luciana Alves Rodrigues dos Santos, Campos, Fernanda Fraga, Mendes, Isolda Castro, Beraldo, Heloisa, de Souza-Fagundes, Elaine Maria, Cisalpino, Patrícia Silva, Rosa, Carlos Augusto, de Almeida Alves, Tânia Maria, de Sá, Nívea Pereira, Zani, Carlos Leomar
• Format: Article
• Language: English
• Subjects: antimicrobial agents; lapachol; Paracoccidioides
• ISSN: 1678-8060

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.