RESUMO
Chromoblastomycosis (CBM) is a chronic subcutaneous infection caused by melanotic fungi, affecting mainly rural workers in tropical and subtropical regions. Secondary bacterial infections (SBIs) in CBM lesions bring complications to the disease, but little is known about the agents involved. Fungal and bacterial identification and epidemiological profile of 50 patients with CBM were analyzed in this study. Bacteria were tested for susceptibility to antibacterial drugs. Fonseacea pedrosoi and Rhinocladiella aquaspersa were the fungal agents isolated. 88% of the patients presented SBI. Gram-positive bacteria coinfected mainly upper limbs, and Gram-negative bacteria were more isolated from lower limbs. Streptococcus pyogenes and mixed bacterial microbiota were associated with severe lesions. Staphylococcus aureus was associated with mixed infections and consequently with the severity of the infection. Resistance to ß-lactams and methicillin was detected. Our results emphasize the necessity of bacterial culture and susceptibility testing as part of routine monitoring CBM cases.
Assuntos
Cromoblastomicose/microbiologia , Coinfecção/microbiologia , Idoso , Antibacterianos/farmacologia , Ascomicetos/isolamento & purificação , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Brasil/epidemiologia , Cromoblastomicose/diagnóstico , Cromoblastomicose/epidemiologia , Coinfecção/diagnóstico , Coinfecção/epidemiologia , Farmacorresistência Bacteriana , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Microbiota , Pessoa de Meia-Idade , Especificidade da EspécieRESUMO
BACKGROUND: The trypanosomatids, such as the protozoan Leishmania spp., have a demand by ergosterol, which is not present in the membrane from mammal cells. The suppression of the synthesis of ergosterol would be a new target of compounds with leishmanicidal activity, and bistriazole has shown trypanocidal activity by this mechanism. The incidence of fungal infections has increased at an alarming rate over the last decades. This is related both to the growing population of immune-compromised individuals and to the emergence of strains that are resistant to available antifungals. Therefore, there is a challenge for the search of potential new antifungal agents. OBJECTIVE: The study aimed to synthesize 1,4-disubstituted-1,2,3-bistriazoles by optimized copper( I)-catalyzed alkyne-azide cycloaddition (CuAAC) and evaluate their antifungal and antitrypanosomastid activities. METHOD: The synthesis of symmetrical bistriazoles with diazides as spacers was planned to be performed following the CuAAC reaction strategy. For evaluation of best conditions for the synthesis of symmetrical bistriazoles hex-1-yne 2 was chosen as leading compound, and a variety of catalysts were employed, choosing (3:1) alkyne:diazide stoichiometric relationship employing CuSO4.5H2O as the best condition. For the preparation of diversity in the synthesis of symmetrical bistriazoles, a 1,3-diazide-propan-2-ol 1a and 1,3-diazidepropane 1b were reacted with seven different alkynes, furnishing eleven symmetrical bistriazoles 9-13a,b and 14a. All compounds were essayed to cultures of promastigotes of L. amazonensis (1 x 106 cells mL-1) in the range of 0.10 - 40.00 µg mL-1 and incubated at 25ºC. After 72 h of incubation, the surviving parasites were counted. For antifungal assay, the minimum inhibitory concentrations (MIC) for yeasts and filamentous fungi were determined. Each compound was tested in 10 serial final concentrations (64 to 0.125 µg mL-1). RESULTS: Eleven 1,4-disubstituted-1,2,3-bistriazoles were synthesized and their structures were confirmed by IR, 1H and 13C-NMR and Mass spectral analysis. The antifungal and antitrypanosomastid activities were evaluated. The best result to antifungal activity was reached by bistriazole 11a that showed the same MIC of fluconazole (32 µg mL-1) against Candida krusei ATCC 6258, an emerging and potentially multidrug-resistant fungal pathogen. Due to their intrinsically biological activity versatility, five derivatives compounds showed leishmanicidal inhibitory activity between 15.0 and 20.0% at concentrations of 20 and 40.0 µg mL-1. Among these compounds the derivative 13a showed best IC50 value of 63.34 µg mL-1 (182.86 µM). CONCLUSION: The preliminary and promising results suggest that bistriazole derivatives, especially compound 13a, could represent an innovative scaffold for further studies and development of new antifungal and anti-parasitic drug candidates.
Assuntos
Alcinos/química , Azidas/química , Cobre/química , Fungos/efeitos dos fármacos , Leishmania/efeitos dos fármacos , Triazóis/química , Triazóis/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/farmacologia , Catálise , Técnicas de Química Sintética , Tripanossomicidas/síntese química , Tripanossomicidas/química , Tripanossomicidas/farmacologiaRESUMO
The in vitro antifungal activity of nine dirutheniumpentadithiocarbamate complexes C1-C9 was investigated and assessed for its activity against four different fungal species with clinical interest and related to invasive fungal infections (IFIs), such as Candida spp. [C. albicans (two clinical isolates), C. glabrata, C. krusei, C. parapsolisis, C. tropicalis, C.dubliniensis (six clinical isolates)], Paracoccidioides brasiliensis (seven clinical isolates), Cryptococcus neoformans and Sporothrix schenckii. All synthesized complexes C1-C9 and also the free ligands L1-L9 were submitted to in vitro tests against those fungi and the results are very promising, since some of the obtained MIC (minimal inhibitory concentration) values were very low (from 10-6 mol mL-1 to 10-8 mol mL-1) against all investigated clinically relevant fungal pathogens, except for C. glabrata, that the MIC values are close to the ones obtained for fluconazole, the standard antifungal agent tested. Preliminary structure-activity relations (SAR) might be suggested and a strong influence from steric and lipophilic parameters in the antifungal activity can be noticed. Cytotoxicity assays (IC50) showed that the complexes are not as toxic (IC50 values are much higher-30 to 200 fold-than MIC values). These ruthenium complexes are very promising lead compounds for novel antifungal drug development, especially in IFIs, one of most harmful emerging infection diseases (EIDs).