title: The antimicrobial activity of lapachol and its thiosemicarbazone and semicarbazone derivatives.
abstract: 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.
authors.affiliation: Fiocruz, Centro de Pesquisas René Rachou, Laboratório de Química de Produtos Naturais, Belo Horizonte, MG, Brasil.
authors.forename: Marina Azevêdo
authors.initials: MA
authors.lastname: Souza
authors.forename: Susana
authors.initials: S
authors.lastname: Johann
authors.forename: Luciana Alves Rodrigues dos Santos
authors.initials: LA
authors.lastname: Lima
authors.forename: Fernanda Fraga
authors.initials: FF
authors.lastname: Campos
authors.forename: Isolda Castro
authors.initials: IC
authors.lastname: Mendes
authors.forename: Heloisa
authors.initials: H
authors.lastname: Beraldo
authors.forename: Elaine Maria de
authors.initials: EM
authors.lastname: Souza-Fagundes
authors.forename: Patrícia Silva
authors.initials: PS
authors.lastname: Cisalpino
authors.forename: Carlos Augusto
authors.initials: CA
authors.lastname: Rosa
authors.forename: Tânia Maria de Almeida
authors.initials: TM
authors.lastname: Alves
authors.forename: Nívea Pereira
authors.initials: NP
authors.lastname: de Sá
authors.forename: Carlos Leomar
authors.initials: CL
authors.lastname: Zani
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D056285:Cryptococcus gattii / Q000187:drug effects; D013293:Enterococcus faecalis / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009285:Naphthoquinones / Q000494:pharmacology*; D010228:Paracoccidioides / Q000187:drug effects; D012664:Semicarbazones / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects; D013882:Thiosemicarbazones / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D009285:Naphthoquinones; D012664:Semicarbazones; D013882:Thiosemicarbazones; C008252:lapachol