The treatment of leishmaniasis includes pentavalent antimony drugs but, because of the side effects, toxicity and cases of treatment failure or resistance, the search of new antileishmanial compounds are necessary. The aims of this study were to evaluate and compare the in vitro antileishmanial activity of four green tea catechins, and to assess the efficacy of topical (−)-epigallocatechin gallate in a cutaneous leishmaniasis model. The antileishmanial activity of green tea catechins was evaluated against intracellular amastigotes, and cytotoxicity was performed with human monocytic cell line. BALB/c mice were infected in the ear dermis with Leishmania (Leishmania) amazonensis and treated with topical 15% (−)-epigallocatechin gallate, intraperitoneal Glucantime, and control group. The efficacy of treatments was evaluated by quantifying the parasite burden and by measuring the lesions size. (−)-Epigallocatechin gallate and (−)-epigallocatechin were the most active compounds with IC50 values <59.6 µg/mL and with a selectivity index >1. Topical treatment with (−)-epigallocatechin gallate decreased significantly both lesion size and parasite burden (80.4% inhibition) compared to control group (p < 0.05), and moreover (−)-epigallocatechin gallate showed a similar efficacy to Glucantime (85.1% inhibition), the reference drug for leishmaniasis treatment.

The diagnosis of American tegumentary leishmaniasis (ATL) still requires the design of more effective tools. Leishmania (Viannia) braziliensis is the causal agent of the 90% of Argentinean ATL cases. Considering the current knowledge, an ELISA based crude antigen (CA) for the diagnosis was designed. Ninety-nine subjects diagnosed as ATL, 27 as no-ATL, and 84 donors from non-ATL-endemic areas were included in this study. The current ATL diagnosis was based four techniques, dermal smear microscopic examination (parasitological test), PCR, Leishmanin skin test, and clinical records. We obtained CA extracts from promastigotes and amastigotes from macrophage cultures of different zymodemes of endemic Leishmania species circulating in the study area. Crude antigens from the 'local' main zymodeme of L. (V.) braziliensis showed the highest reactivity against anti-Leishmania antibodies compared to the other included species. The CA of amastigotes of this zymodeme was 3.4 fold more reactive than promastigotes one. Moreover, amastigote-membrane CA (MCA) were 3.6 fold more reactive than the soluble antigens. The MCA-ELISA reached a sensitivity and specificity of 98% (CI = 94.7%-100%) and 63.6% (53.9-73.1), respectively. When anti-Trypanosoma cruzi reactive sera were excluded, the specificity reached 98.4% (94.4-100), while the sensitivity was similar, with a positive predictive value (PV) of 98.6% (94.6-100) and negative PV of 96.3% (91.6-100). The performance of the MCA-ELISA results strongly contribute to the final diagnostic decision, since a non-reactive serological result almost discards the suspected ATL, because of its high negative PV. The developed PLOS ONE

Seventeen sesquiterpene lactones (SLs) isolated from five species of the tribe Vernonieae were evaluated for their in vitro activity against promastigotes of Leishmania amazonensis and Leishmania braziliensis. Additionally, a quantitative structure activity relationship has been made, since all these natural compounds were found to have potent to mild antileishmanial properties. The most active compounds against L. braziliensis were 16 and 17 (IC values 1.45 and 1.34 μM, respectively), followed by compound 15 with IC value of 1.60 μM against L. amazonensis. The three glaucolide-type SLs (4-6) were the least active against both parasites. The computational study allowed us to establish that lipophilicity and polarisability play an important role in the antiparasitic activity. This is the first report of the known germacradiendiolides 16 and 17 from Elephantopus mollis. The activity data of the compounds 1-17 assayed against Leishmania parasites are reported here for the first time.

Vernonanthura nebularum (Cabrera) H. Rob. (Asteraceae), an endemic species from the north of Argentina, is a rich source of elephantopus-type sesquiterpene lactones. These compounds have proved to be promising antiparasitic agents, but there is no report about their action against pest insects. In this work we studied for the first time the antifeedant and toxic effects of V. nebularum natural products against the fall army warm Spodoptera frugiperda Smith and the oviposition deterrent activity against the fruit fly Ceratitis capitata Wiedemann. As a result, we found that extracts, fractions composed of sesquiterpene lactones and pure sesquiterpene lactones altered larval feeding behavior in the food choice test. Nutritional parameters of S . frugiperda larvae were also affected. Fraction II (300 μg/g of diet.), containing compounds 1 , 2 and 3 , was the most toxic substance with 80% pupal mortality and wing malformations in adults. In oviposition deterrent experiments against Ceratitis capitata , we observed a moderate effect at 30 μg/cm 2 of the test compound. The most active substances were the methanolic extract, dichloromethane subextract and lactone 2 . According to our results, V. nebularum natural products could be used for maximizing the effectiveness and specificity in future insecticide design with specific or multiple target sites, while ensuring the economic and ecological sustainability, in addition to combat the increasing resistance rates developed by synthetic pesticides.