This study examined whether the antidermatophytic activity of essential oils (EOs) can be used as an indicator for the discovery of active natural products against Leishmania amazonensis. The aerial parts of seven plants were hydrodistilled. Using broth microdilution techniques, the obtained EOs were tested against three strains of dermatophytes (Trichophyton mentagrophytes, Microsporum gypseum and Microsporum canis). To compare the EOs antifungal and antiparasitic effects, the EOs activities against axenic amastigotes of L. amazonensis were concurrently evaluated. For the most promising EOs, their antileishmanial activities against parasites infecting peritoneal macrophages of BALB/c mice were measured. The most interesting antifungal candidates were the EOs from Cymbopogon citratus, Otacanthus azureus and Protium heptaphyllum, whereas O. azureus, Piper hispidum and P. heptaphyllum EOs exhibited the lowest 50% inhibitory concentration (IC50) values against axenic amastigotes, thus revealing a certain correspondence between both activities. The P. hispidum EO was identified as the most promising product in the results from the infected macrophages model (IC50: 4.7 µg/mL, safety index: 8). The most abundant compounds found in this EO were sesquiterpenes, notably curzerene and furanodiene. Eventually, the evaluation of the antidermatophytic activity of EOs appears to be an efficient method for identifying new potential drugs for the treatment of L. amazonensis.

The effectiveness of methylene blue (MB) combined with pyrimethamine (PYR), chloroquine (CQ) or quinine (Q) was examined in a classical four-day suppressive test against a causative agent of rodent malaria, Plasmodium berghei. A marked potentiation was observed when MB was administered at a non-curative dose of 15 mg/kg/day in combination with PYR (0.19 mg/kg/day) or Q (25 mg/kg/day). No synergy was found between MB (15 mg/Kg) and CQ (0.75 mg/Kg). Our results suggest that the combination of MB with PYR or Q may improve the efficacy of these currently used antimalarial drugs.

A series of ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl)-2-propen-1-one derivatives were synthesized and tested for in vitro leishmanicidal activity against amastigotes of Leishmania amazonensis in axenical cultures and murine infected macrophages. Structure-activity relationships demonstrated the importance of a radical methoxy at position R3', R4' and R5'. (2E)-3-(3,4,5-trimethoxy-phenyl)-1-(3,6,7-trimethyl-1,4-dioxy-quinoxalin-2-yl)-propenone was the most active. Cytotoxicity on macrophages revealed that this product was almost six times more active than toxic.

En 1881, Ehrlich reportó el azul de metileno como el primer antimalárico sintético, pero dejo de ser empleado con este propósito; el debe ser reconsiderado pues son necesarias con urgencia nuevas alternativas de bajo costo, en el arsenal de medicamentos antimaláricos. En este trabajo la actividad antimalárica del azul de metileno es evaluada in vivo frente a parásitos de malaria murina. Una dosis de 15 mg/kg/día inhibe el 50% del crecimiento eritrocítico parasitario de Plasmodium berghei y P. yoelii nigeriensis, en tanto que es prácticamente inactivo frente a los estadios hepáticos de P. yoelii yoelii. Sobre un cultivo de la línea celular linfoblástica BJAB, el azul de metileno es 20 veces más citotóxico que la cloroquina, no obstante el azul de metileno presenta valores de índice de selectividad del mismo nivel que la cloroquina, frente a varias cepas de P. falciparum de diferentes niveles de sensibilidad y provenientes de diferentes lugares geográficos.

Methilene blue was reported as the first synthetic antimalarial by Ehrlich in 1881. It is currently no longer used for that purpose but it should be reconsidered since new economic alternatives are urgently needed in the arsenal of antimalarial drugs. The antimalarial activity of methylene blue is investigated here in vivo against rodent malaria parasites. 15 mg/kg daily dose of methylene blue inhibits 50% of the erythrocytic parasite growth of Plasmodium berghei and P. yoelii nigeriensis, while on hepatic stages of P. yoelii yoelii is almost inactive. In cell culture experiments with the lymphoblast-like BJAB cells line, it is 20 times more cytotoxic than chloroquine. Nevertheless, methylene blue shows a similar selectivity index as chloroquine against strains of different level of sensitivity of P. falciparum original from different geographical areas.