Toxocara canis: anthelmintic activity of quinone derivatives in murine toxocarosis.

Human toxocarosis is a chronic tissue parasitosis most often caused by Toxocara canis. The seroprevalence can reach up to 50%, especially among children and adolescents. The anthelmintics used in the treatment have moderate efficacy. The aim of this study was to evaluate the in vitro and in vivo anthelmintic activity of quinones and their derivatives against T. canis larvae and the cytotoxicity of the larvicidal compounds. The compounds were evaluated at 1 mg mL(-1) concentration in microculture plates containing third stage larvae in an Roswell Park Memorial Institute (RPMI) 1640 environment, incubated at 37 °C in 5% CO2 tension for 48 h. Five naphthoxiranes were selected for the cytotoxicity analysis. The cell viability evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays using murine peritoneal macrophages isolated from C57BL/6 mice revealed that the naphthoxiranes (1 and 3) were less cytotoxic at a concentration of 0.05 mg mL(-1). The efficacy of naphthoxiranes (1 and 3) was examined in murine toxocarosis also. The anthelmintic activity was examined by evaluating the number of larvae in the brain, carcass, liver, lungs, heart, kidneys and eyes. Compound (3) demonstrated anthelmintic activity similar to that of albendazole by decreasing the number of larvae in the organs of mice and thus could form the basis of the development of a new anthelmintic drug.

ß-lapachone and α-nor-lapachone modulate Candida albicans viability and virulence factors.

BACKGROUND: Candida albicans is the most important fungal pathogen that causes infections in humans, and the search for new therapeutic strategies for its treatment is essential. OBJECTIVE: The aim of this study was to evaluate the activity of seven naphthoquinones (ß-lapachone, ß-nor-lapachone, bromide-ß-lapachone, hydroxy-ß-lapachone, α-lapachone, α-nor-lapachone and α-xyloidone) on the growth of a fluconazole-resistant C. albicans oral clinical isolate and the effects of these compounds on the viability of mammalian cells, on yeast's morphogenesis, biofilm formation and cell wall mannoproteins availability. RESULTS: All the compounds were able to completely inhibit the yeast growth. ß-lapachone and α-nor-lapachone were the less cytotoxic compounds against L929 and RAW 264.7 cells. At IC50, ß-lapachone inhibited morphogenesis in 92%, while the treatment of yeast cells with α-nor-lapachone decreased yeast-to-hyphae transition in 42%. At 50µg/ml, ß-lapachone inhibited biofilm formation by 84%, whereas α-nor-lapachone reduced biofilm formation by 64%. The treatment of yeast cells with ß-lapachone decreased cell wall mannoproteins availability in 28.5%, while α-nor-lapachone was not able to interfere on this virulence factor. Taken together, data show that ß-lapachone and α-nor-lapachone exhibited in vitro cytotoxicity against a fluconazole-resistant C. albicans strain, thus demonstrating to be promising candidates to be used in the treatment of infections caused by this fungus.

In vitro activity of Brazilian medicinal plants, naturally occurring naphthoquinones and their analogues, against methicillin-resistant Staphylococcus aureus.

Fourteen extracts from Brazilian traditional medicinal plants used to treat infectious diseases were used to look for potential antimicrobial activity against multiresistant bacteria of medical importance. Staphylococcus aureus strains were susceptible to extracts of Punica granatum and Tabebuia avellanedae. The minimum inhibitory concentrations (MICs) of the total extracts and of additional fractions of these plants were determined by employing strains of methicillin-resistant (MRSA) and -sensitive (MSSA) S. aureus, including isolates of the PFGE clone A, which is prevalent in Brazil and two ATCC reference strains. A mixture of ellagitannins isolated from P. granatum and two naphthoquinones isolated from T. avellanedae demonstrated antibacterial activity against all S. aureus strains tested. Semi-synthetic furanonaphthoquinones (FNQs) showed lower MICs than those exhibited by natural occurring naphthoquinones. The results indicate that these natural products can be effective potential candidates for the development of new strategies to treat MRSA infections.

Evaluation of some organic compounds on bloodstream forms of Trypanosoma cruzi

Accidental transmission of Chagas' disease to man by blood transfusion is a serious problem in Latin-America. This paper describes the testing of several synthetic, semi-synthetic, and natural compounds for their activity against blood trypomastigotes in vitro at 4-C. The compounds embody several types of chemical structures: benzoquinone, naphthoquinone, anthracenequinone, phenanthrenequinone, imidazole, piperazine, quinoline, xanthene, and simple benzenic and naphthalenic derivates. Some of them are for the first time tested against Trypanosoma cruzi. The toxic effect these compounds on this parasite was done by two quite distinct sets of experiments. In one set, the compounds were added to infected blood as ethanolic solution. In this situation the most active one was a furan-1, 2-naphthoquinone, in the same range as gentian violet, a new fact to be considered in the assessment of structure-activity relationships in this class of compounds. In other set, we tentatively evaluated the biological activity of water insoluble compounds by adding them in a pure form without solvent into infected blood. In this way some appear to be very active and it was postulated that the effectiveness of such compounds must result from interactions between them and specific blood components