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.

Três complexos inéditos do tipo [Cu(HL)Cl2] foram obtidos com N(4)-orto (H2Bz4oT, HL1), N(4)-meta (H2Bz4mT, HL2) e N(4)-para-toluil-2-benzoilpiridina tiossemicarbazona (H2Bz4pT, HL3), nos quais a tiossemicarbazona coordena-se ao metal por meio do sistema quelante Npy-N-S. H2Bz4pT (HL3) cristaliza-se no grupo espacial P1, a = 9,509(3) Å, b = 9,807(4) Å, c = 11,564(4) Å; alfa = 100,76(2)°, beta = 105,99(2)°, gama = 114,59(2)°. Tanto as tiossemicarbazonas quanto seus complexos de cobre(II) apresentaram atividade antifúngica pronunciada contra Candida albicans, com valores baixos de concentração inibitória mínima (CIM), entre 8 e 0,3 µg mL-1 (23 a 0,7 µmol L-1) para as tiossemicarbazonas e entre 1 e 0,1 µg mL-1 (2 a 0,3 µmol L-1) para os complexos. Nossos resultados sugerem que a coordenação ao cobre constitui estratégia interessante de redução da dose necessária à atividade.

Three new copper complexes of general formula [Cu(HL)Cl2] have been obtained with N(4)-ortho (H2Bz4oT, HL1), N(4)-meta (H2Bz4mT, HL2) and N(4)-para-tolyl-2-benzoylpyridine thiosemicarbazone (H2Bz4pT, HL3), in which the thiosemicarbazone attaches to the metal through the Npy-N-S chelating system. H2Bz4pT (HL3) crystallizes in the P1 space group, with a = 9.509(3) Å, b = 9.807(4) Å, c = 11.564(4) Å; alpha = 100.76(2)°, beta = 105.99(2)°, gamma = 114.59(2)°. The thiosemicarbazones and their copper(II) complexes exhibit high antifungal activities against Candida albicans with low values of minimum inhibitory concentration (MIC), in the 8-0.3 µg mL-1 (23 - 0.7 µmol L-1) range for the free bases and in the 1-0.1 µg mL-1 (2 - 0.3 µmol L-1) range for the complexes. Our results suggest that coordination to copper(II) could be an interesting strategy for dose reduction.

O presente relato de caso, descreve nossa experiência diagnóstica e terapêutica com um paciente que apresentou manifestações clínicas, radiológicas e tomográficas de paracoccidioidomicose comprometendo os pulmões, cérebro e, particularmente, a medula espinhal. Além da raridade do caso, chama-se a atenção para a extrema dificuldade na elucidação diagnóstica definitiva, obtida somente após laminectomia e biópsia cirúrgica de tumoração intramedular ao nível de C5. O paciente recebeu duas séries de tratamento com, ketoconazol (400 a 600 mg/dia). No início de ambas apresentou crise convulsiva tônico-clônica. Especula-se sobre uma possível resposta inflamatória perigranulomatosa intracerebral, relacionada à intervenção terapêutica, ainda sem relato na literatura.

It is reported our diagnosis and therapeutical experience with a patient that presented clinical, radiological and tomographical manifestations of paracoccidioidomycosis with involvement of lungs, brain and spinal cord. Besides being a rare case the authors call attention for the extreme difficulty in defining the final diagnosis, which was achieved only after laminectomy and surgical biopsy of the intra spinal cord tumor at the C5 level. The patient received two series of treatment with ketoconazole (400-600 mg/day). After both the patient presented tonic and clonic convulsive disorders. We speculated about a possible perigranulomatous inflammatory response related to the therapeutical intervention, not yet described in literature.