ABSTRACT Among the neglected diseases, American cutaneous leishmaniasis (ACL) still remains highly endemic in some tropical regions. The currently available drugs for treatment are highly toxic, prompting the search for new therapeutic options. The aim of this study was to evaluate the toxic potential of dillapiole n-butyl ether (DBE) against Leishmania amazonensis and L. guyanensis, as well as its toxicity on human peripheral blood mononuclear cells (PBMCs) in vitro. For cell cytotoxicity, concentrations of DBE that ranged from 7.8 to 500 µM were used for 48 and 72 h. For the evaluation of the antileishmanial activity, DBE was tested at concentrations of 0.28 to 18 µM for 24, 48, and 72 h. A value of 36 µM was used for the amastigote assay. The selectivity index (SI) was determined by dividing the CC50/IC50 (macrophages/promastigotes). DBE exhibited a CC50 of 203.9 ± 0.5 µM in 72 h. DBE inhibited promastigote forms with an IC50 of 3.0 µM for both Leishmania species for 72 h. The standard, Pentacarinat®, showed an IC50 of 2.9 µM and 0.3 µM, respectively. The SI of DBE for both species was 67.9 for 72 h. DBE inhibited intracellular forms of L. amazonensis by 65.5% after 48 h. In molecular modeling, DLpOl-F showed two hydrogen bonds (SER418 and 421). DBE demonstrated promising in vitro antileishmanial potential.

RESUMO Dentre as doenças negligenciadas, a leishmaniose cutânea americana (LCA) continua sendo altamente endêmica em algumas regiões tropicais. Os medicamentos disponíveis atualmente para o tratamento apresentam elevada toxicidade, o que torna a busca de novas opções terapêuticas necessária. O objetivo do estudo foi avaliar o potencial tóxico do éter n-butil dilapiol (EBD) contra Leishmania amazonensis e L. guyanensis e a sua toxicidade em células mononucleares do sangue periférico humano (CMSP) in vitro. Para a citotoxicidade celular, utilizou-se concentrações de 7,8 a 500 µM por 48 e 72 h. A atividade antileishmania do EBD foi testada em concentrações de 0,28 a 18 µM, por 24, 48 e 72 h. Para o ensaio em amastigotas usou-se um valor de 36 µM. O índice de seletividade (IS) foi determinado pela divisão CC50/CI50 (macrófagos/promastigotas). O EBD mostrou em células uma CC50 de 203,9 ± 0,5 µM em 72 h. O EBD inibiu as formas promastigotas com uma CI50 de 3,0 µM para ambas espécies de Leishmania por 72 h, já o padrão Pentacarinat® apresentou uma CI50 de 2,9 µM e 0,3 µM, respectivamente. O IS do EBD para as duas espécies foi de 67,9 por 72 h. O EBD inibiu as formas intracelulares de L. amazonensis com 65,5% por 48 h. Na modelagem molecular, o DLpOl-F aparece com duas ligações de hidrogênio (SER418 e 421). O EBD demostrou um potencial antileishmania promissor in vitro.

Abstract INTRODUCTION: Chagas disease (CD) prevention and control rely on studies of its distribution, characteristics of individuals affected and mode of transmission. CD data in Brazil are scarce; a retrospective analysis of the clinical characteristics of 80 patients treated at the Clinical Hospital of UNICAMP, Campinas, Brazil, was performed. METHODS: Patient data records were analyzed. RESULTS: Thirty percent of the patients probably got infected through vector-borne transmission, 65% came from endemic areas, a predominance of cardiac and cardiodigestive forms was found among males, and the cardiac form prevailed (51%). CONCLUSIONS: The results update the view on the epidemiology of CD in Campinas, Brazil.

The 70 kDa heat shock protein (HSP70) is a molecular chaperone that assists the parasite Leishmania in returning to homeostasis after being subjected to different types of stress during its life cycle. In the present study, we evaluated the effects of HSP70 transfection of L. amazonensis promastigotes (pTEX-HSP70) in terms of morphology, resistance, infectivity and mitochondrial bioenergetics. The pTEX-HSP70 promastigotes showed no ultrastructural morphological changes compared to control parasites. Interestingly, the pTEX-HSP70 promastigotes are resistant to heat shock, H2O2-induced oxidative stress and hyperbaric environments. Regarding the bioenergetics parameters, the pTEX-HSP70 parasites had higher respiratory rates and released less H2O2 than the control parasites. Nevertheless, the infectivity capacity of the parasites did not change, as verified by the infection of murine peritoneal macrophages and human macrophages, as well as the infection of BALB/c mice. Together, these results indicate that the overexpression of HSP70 protects L. amazonensis from stress, but does not interfere with its infective capacity.

Phytochemical investigation of the hexane extract from the stem of Xylopia laevigata led to the isolation of the ent-kaurane diterpenoids, ent-kaur-16-en-19-oic acid, 4-epi-kaurenic acid, ent-16β-hydroxy-17-acetoxy-kauran-19-al, ent-3β-hydroxy-kaur-16-en-19-oic acid, and ent-16β,17-dihydroxy-kauran-19-oic acid, as well as spathulenol and a mixture of β-sitosterol, stigmasterol and campesterol. The identification of the compounds was performed on the basis of spectrometric methods including GC-MS, IR, and 1D and 2D NMR. Potent larvicidal activity against Aedes aegypti larvae with LC50 of 62.7 µg mL-1 was found for ent-3β-hydroxy-kaur-16-en-19-oic acid. This compound also showed significant antifungal activity against Candida glabrata and Candida dubliniensis with MIC values of 62.5 µg mL-1.