Frequency of F508del Variant in Patients with Cystic Fibrosis from Paraguay

Abstract Cystic fibrosis (CF) is an autosomal recessive disorder and is caused by variants in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. We aimed to study the frequency of the F508del variant, the most common variant worldwide, in patients with CF from Paraguay. The frequency of the F508del variant in Paraguayan patients with a clinical diagnosis of CF was assessed using a polymerase chain reaction followed by the sequencing of the PCR products. 43 of the 86 patients (50%) were homozygous for the F508del variant, 28 were heterozygous (32.56%), and the remaining 15 (17.44%) were non-carriers. In terms of alleles, there were 114 mutated (114/172 or 66.28%) and 58 did not correspond to this variant (58/172 or 33.72%). This is the first study of the frequency of the F508del variant in patients with CF in Paraguay. This information is of utmost relevance when planning and offering treatments from health services.

Solid Nanomedicines of Nifurtimox and Benznidazole for the Oral Treatment of Chagas Disease.

Chagas disease (CD) is a parasitic zoonosis endemic in Central and South America affecting nearly 10 million people, with 100 million people at high risk of contracting the disease. Treatment is only effective when received at the early stages of the disease and it involved two drugs (nifurtimox (NFX) and benznidazole (BNZ)). Both treatments require multiple daily administrations of high doses, suffer from variable efficacy and insufficient efficacy in chronic CD, many side effects, and a very long duration of treatment that results in poor compliance, while combined available therapies that lead to reduced duration of treatment are not available and polypharmacy reduces compliance and increases the cost further. Here we present self-nanoemulsified drug delivery systems (SNEDDS) able to produce easily scalable combined formulations of NFX and BNZ that can allow for tailoring of the dose and can be easily converted to oral solid dosage form by impregnation on mesoporous silica particles. SNEDDS demonstrated an enhanced solubilisation capacity for both drugs as demonstrated by flow-through studies and in vitro lipolysis studies. High loading of SNEDDS to Syloid 244 and 3050 silicas (2:1 w/w) allowed clinically translatable amounts of both NFX and BNZ to be loaded. Tablets prepared from NFX-BNZ combined SNEDDS loaded on Syloid 3050 silicas demonstration near complete dissolution in the flow through cell apparatus compared to NFX and BNZ commercial tablets respectively (Lampit® and Rochagan®). NFX-BNZ-SNEDDS demonstrated nanomolar efficacy in epimastigotes and amastigotes of T. cruzi with acceptable selectivity indexes and demonstrated enhanced survival and reduced parasitaemia in acute murine experimental models of CD. Thus, the results presented here illustrate the ability for an easily scalable and personalised combination oral therapy prepared from GRAS excipients, enabling treatment access worldwide for the treatment of CD.

Synthesis, trypanocidal and anti-leishmania activity of new triazole-lapachol and nor-lapachol hybrids.

A new library of twenty triazole-lapachol and nor-lapachol derivatives was synthesized. The compounds were evaluated against the epimastigotes form of Trypanosoma cruzi and promastigotes of Leishmania braziliensis and L. infantum. The cytotoxicity of the compounds was determined on murine fibroblasts and used to assess the selectivity index. The introduction of triazole rings in the naphthoquinone derivatives improved activity against the parasitic protozoa T. cruzi and Leishmania species. Some of the derivatives were three to six times more potent than benznidazole against T. cruzi, with similar or slightly better selectivity indexes. The results against L. braziliensis showed that the derivatives 5b and 5e were the most selective compounds. However, they were less selective than the reference compound, miltefosine. Among all products, the derivative 3a was the most selective compound against L. infantum. Nevertheless, it was less potent and less selective than miltefosine. Also, the minimum inhibitory concentration values of the derivatives against nine different bacteria were determined. Moderate antibacterial activity was observed for compound 5c against Staphylococcus aureus.

Ximenia americana L. enhances the antibiotic activity and inhibit the development of kinetoplastid parasites.

OBJECTIVE: The objective of this work was evaluate the cytotoxic, leishmanicidal and tripanocidal activity, as well as to evaluate its antimicrobial and modulatory activity in association with different antibiotics of the hydroethanolic extract of the Ximenia Americana stem bark (EHXA). METHOD: In vitro tests against Trypanosoma cruzi, Leishmania sp. and citotoxicity were performed. The evaluation of the antibacterial and bacterial resistance modulatory effect was given by the microdilution method. RESULTS: The chemical profile show different classes of compounds with significant presence of quercetrin and caffeic acid. The EHXA demonstrated activity only in the concentration of 1000 µg/mL against the L. infantum and L. brasiliensis promastigotes, causing mortality percentage of 40.66 and 27.62%, respectively. The extract presented a significant toxicity only in the concentration of 1000 µg/mL, causing a mortality of 55.42% of fibroblasts. The antibacterial activity of the EHXA demonstrated a MIC value ≥1024 µg/mL against all the tested bacteria. However, in the modulation assay with EHXA in association with different antibiotics the extract had a synergistic effect against S. aureus strains when associated with norfloxacin. CONCLUSION: The results of this investigation demonstrate for the first time the chemical composition of the hydroethanolic extract of the Ximenia Americana stem bark, your potential antiparasitic and modulatory effect. The low cytotoxic and biological potential against S. aureus open therapeutic perspectives against leishmaniosis and bacterial infections.

The use of herbs against neglected diseases: Evaluation of in vitro leishmanicidal and trypanocidal activity of Stryphnodendron rotundifolium Mart.

The evaluation of the leishmanicidal and trypanocidal activity of the hydroalcoholic extract of the bark of Stryphnodendron rotundifolium Mart. (EHCSR) was carried out to find an alternative treatment for parasitic diseases. EHCSR was prepared and used at four different concentrations (1000, 500, 250, 125 µg/mL) in in vitro assays for activity against Leishmania promastigotes using the species Leishmania brasiliensis and Leishmania infantum and for trypanocidal activity using the epimastigotes of Trypanosoma cruzi. We also tested EHCSR for cytotoxicity against adhered cultured Murine J774 fibroblasts. The tests were performed in triplicate, and the percent mortality of parasites, IC50 and percent toxicity were determined. With regard to anti-leishmania activity against L. infantum, there was a mean mortality of 45% at all concentrations, and against L. brasiliensis, a substantial effect was seen at 1000 µg/mL with 56.38% mortality, where the IC50 values were 1338.76 and 987.35 µg/mL, respectively. Trypanocidal activity was notably high at 1000 µg/mL extract with 82.31% mortality of epimastigotes. Cytotoxicity at the highest extract concentrations of 500 and 1000 µg/mL was respectively 75.12% and 94.14%, with IC50 = 190.24 µg/mL. Despite that the extract has anti-parasitic activity, its substantial cytotoxicity against fibroblasts cells makes its systemic use nonviable as a therapeutic alternative.

Multi-Anti-Parasitic Activity of Arylidene Ketones and Thiazolidene Hydrazines against Trypanosoma cruzi and Leishmania spp.

A series of fifty arylideneketones and thiazolidenehydrazines was evaluated against Leishmania infantum and Leishmania braziliensis. Furthermore, new simplified thiazolidenehydrazine derivatives were evaluated against Trypanosoma cruzi. The cytotoxicity of the active compounds on non-infected fibroblasts or macrophages was established in vitro to evaluate the selectivity of their anti-parasitic effects. Seven thiazolidenehydrazine derivatives and ten arylideneketones had good activity against the three parasites. The IC50 values for T. cruzi and Leishmania spp. ranged from 90 nM-25 µM. Eight compounds had multi-trypanocidal activity against T. cruzi and Leishmania spp. (the etiological agents of cutaneous and visceral forms). The selectivity of these active compounds was better than the three reference drugs: benznidazole, glucantime and miltefosine. They also had low toxicity when tested in vivo on zebrafish. Trying to understand the mechanism of action of these compounds, two possible molecular targets were investigated: triosephosphate isomerase and cruzipain. We also used a molecular stripping approach to elucidate the minimal structural requirements for their anti-T. cruzi activity.

Antiprotozoal Activity of Triazole Derivatives of Dehydroabietic Acid and Oleanolic Acid.

Tropical parasitic diseases such as Chagas disease and leishmaniasis are considered a major public health problem affecting hundreds of millions of people worldwide. As the drugs currently used to treat these diseases have several disadvantages and side effects, there is an urgent need for new drugs with better selectivity and less toxicity. Structural modifications of naturally occurring and synthetic compounds using click chemistry have enabled access to derivatives with promising antiparasitic activity. The antiprotozoal activity of the terpenes dehydroabietic acid, dehydroabietinol, oleanolic acid, and 34 synthetic derivatives were evaluated against epimastigote forms of Trypanosoma cruzi and promastigotes of Leishmaniabraziliensis and Leishmania infantum. The cytotoxicity of the compounds was assessed on NCTC-Clone 929 cells. The activity of the compounds was moderate and the antiparasitic effect was associated with the linker length between the diterpene and the triazole in dehydroabietinol derivatives. For the oleanolic acid derivatives, a free carboxylic acid function led to better antiparasitic activity.

Engineering Oral and Parenteral Amorphous Amphotericin B Formulations against Experimental Trypanosoma cruzi Infections.

Chagas disease (CD) is a parasitic zoonosis endemic in most mainland countries of Central and South America affecting nearly 10 million people, with 100 million people at high risk of contracting the disease. Treatment is only effective if received at the early stages of the disease. Only two drugs (benznidazole and nifurtimox) have so far been marketed, and both share various limitations such as variable efficacy, many side effects, and long duration of treatment, thus reducing compliance. The in vitro and in vivo efficacy of poly-aggregated amphotericin B (AmB), encapsulated poly-aggregated AmB in albumin microspheres (AmB-AME), and dimeric AmB-sodium deoxycholate micelles (AmB-NaDC) was evaluated. Dimeric AmB-NaDC exhibited a promising selectivity index (SI = 3164) against amastigotes, which was much higher than those obtained for licensed drugs (benznidazole and nifurtimox). AmB-AME, but not AmB-NaDC, significantly reduced the parasitemia levels (3.6-fold) in comparison to the control group after parenteral administration at day 7 postinfection. However, the oral administration of AmB-NaDC (10-15 mg/kg/day for 10 days) resulted in a 75% reduction of parasitemia levels and prolonged the survival rate in 100% of the tested animals. Thus, the results presented here illustrate for the first time the oral efficacy of AmB in the treatment of trypanosomiasis. AmB-NaDC is an easily scalable, affordable formulation prepared from GRAS excipients, enabling treatment access worldwide, and therefore it can be regarded as a promising therapy for trypanosomiasis.

In vitro antiprotozoal activity of (S)-cis-Verbenol against Leishmania spp. and Trypanosoma cruzi.

(S)-cis-Verbenol, a monoterpene frequently found as a component of essential oils, was assayed against Leishmania amazonensis, Leishmania infantum, Leishmania brasiliensis and against two strains of Trypanosoma cruzi. The cytotoxicity of the compound was also assayed against human fibroblast cells using a colorimetric method. Benznidazole was used as reference drug against T. cruzi and amphotericin B was used against Leishmania spp. The compound showed good activity against the trypanosomes, being more active against the CL Brenner strain, with an IC50 value of 8.3µg/mL. Against Leishmania, the IC50 values were between 2.1 and 3.8µg/mL. The compound showed no cytotoxicity against human fibroblasts at the concentrations assayed and was 100-500 times more toxic for the parasites than for the human cells, as indicated by the selectivity indexes. The results open interesting perspectives about the potential of (S)-cis-Verbenol and other individual components of essential oils for the treatment of these diseases.

Chemical Characterization and Trypanocidal, Leishmanicidal and Cytotoxicity Potential of Lantana camara L. (Verbenaceae) Essential Oil.

Drug resistance in the treatment of neglected parasitic diseases, such as leishmaniasis and trypanosomiasis, has led to the search and development of alternative drugs from plant origins. In this context, the essential oil extracted by hydro-distillation from Lantana camara leaves was tested against Leishmania braziliensis and Trypanosoma cruzi. The results demonstrated that L. camara essential oil inhibited T. cruzi and L. braziliensis with IC50 of 201.94 µg/mL and 72.31 µg/mL, respectively. L. camara essential oil was found to be toxic to NCTC929 fibroblasts at 500 µg/mL (IC50 = 301.42 µg/mL). The composition of L. camara essential oil analyzed by gas chromatography-mass spectrometry (GC/MS) revealed large amounts of (E)-caryophyllene (23.75%), biciclogermacrene (15.80%), germacrene D (11.73%), terpinolene (6.1%), and sabinene (5.92%), which might be, at least in part, responsible for its activity. Taken together, our results suggest that L. camara essential oil may be an important source of therapeutic agents for the development of alternative drugs against parasitic diseases.

Analysis of bioactivities and chemical composition of Ziziphus joazeiro Mart. using HPLC-DAD.

The aim of this study was to evaluate the chemical profile and antioxidant, antimicrobial and antiparasitic activities of the hydroalcoholic extract of the leaves of Ziziphus joazeiro Mart. (HELZJ). The antioxidant DPPH and FRAP assays and chemical profile were determined by colorimetric methods and HPLC/DAD. The antiparasitic, antibiotic and antibiotic-modifying activity were evaluated by microdilution assays. The HPLC-DAD assay showed the presence of mostly tannins and flavonoids, such as caffeic acid and quercetin. The levels of polyphenols and flavonoids were 183.136 mg/g extract and 7.37 mg/g extract, respectively. DPPH and FRAP showed low antioxidant activity for the extract. The antibacterial and antifungal activities were not of clinical relevance, showing MIC>1024 µg/mL. However, synergism was observed between HELZJ and the antibiotics amikacin and gentamicin, which resulted in decreased bacterial drug resistance. EHFZJ showed low toxicity in fibroblasts in vitro, while antiparasitic results against Trypnosoma cruzi, Leishmania braziliensis and Leishmania infantum were not clinically relevant. Thus, our results indicate that Z. joazeiro Mart. (HELZJ) could be a source of plant-derived natural products that could lead to the development of promising new antibiotic compounds for infectious diseases.

Prevalence of an inherited cancer predisposition syndrome associated with the germ line TP53 R337H mutation in Paraguay.

The tumor suppressor gene TP53 is the most frequently mutated gene in human cancer, and the germline TP53 R337H mutation is the most common mutation reported to date. However, this mutation is associated with a lower cumulative lifetime cancer risk than other mutations in the p53 DNA-binding domain. A detailed statistical analysis of 171,500 DNA tests in Brazilian neonates found that 0.27% of the general population is positive for this mutation, and some of the estimated 200,000 Brazilian R337H carriers in southern and southeastern Brazil have already developed cancer. The present study was designed to estimate R337H prevalence in neighboring Paraguay. To address this question, 10,000 dried blood samples stored in Guthrie cards since 2008 were randomly selected from the Paraguayan municipalities located at the border with Brazil. These samples were tested for R337H mutation using the PCR-restriction fragment length polymorphism assay. This germline mutation was detected in five samples (5/10,000), indicating that the total number of R337H carriers in Paraguay may be as high as 3500. Previous studies have shown that other countries (i.e., Portugal, Spain, and Germany) presented one family with this mutation, leading us to conclude that, besides Brazil and Paraguay, other countries may have multiple families carrying this mutation, which is an inherited syndrome that is difficult to control.

Avaliação da atividade citotóxica e potencial antiparasitário in vitro do a-pineno e carvacrol / Cytotoxic and antiparasitic in vitro activities of a-pinene and carvacrol

A leishmaniose e a doença de Chagas tem sido um grande desafio, no que diz respeito à sua terapêutica. Devido à grande dificuldade de encontrar fármacos que garantam uma ação terapêutica eficiente e menos agressora à espécie humana, diferentes produtos naturais vêm sendo testados. Muitas espécies vegetais foram investigadas quanto à sua ação leishmanicida e tripanocida na expectativa de que seus compostos metabólicos possuam atividade antiparasitária e ausência ou baixa citotoxicidade. Neste estudo sobre bioatividade do a-pineno e carvacrol, avaliaram-se os potenciais leishmanicida e tripanocida. O carvacrol apresentou um percentual de inibição de 38,34% e 74,12% para as formas promastigotas e epimastigotas respectivamente, na concentração de 100µg/mL, apresentando uma citotoxicidade de 21,62%. O a-pineno apresentou 100% e 5,30% de inibição para as formas epimastigota e promastigota na concentração de 100 µg/mL, com citotoxicidade de 87,88%.

Leishmaniasis and Chagas Disease represent a great challenge against the modern therapeutics. Due the high difficult to find new drugs with therapeutic efficacy and low toxicity, several natural products had been screened. Many species of plants were investigated about their leishmanicidal and trypanocidal activities. Some phytocompounds are the a-pinene and carvacrol. In this work, we evaluated the bioactivities of a-pinene and carvacrol against Trypanosoma cruzi and Leishmania braziliensis cell lines. The carvacrol inhibited 38,34% and 74,12% of the promatigote and epimastigote forms, respectively at 100 µg/mL, showing a low cytotoxic activity (21,62%). The O a-pinene inhibited 100% and 5,30% against the epimastigote and promastigote forms respectively, at 100 µg/mL, showing a higher cytotoxic activity (87,88%).

AvaliaþÒo da atividade citotóxica e potencial antiparasitário in vitro do a-pineno e carvacrol / Cytotoxic and antiparasitic in vitro activities of a-pinene and carvacrol

A leishmaniose e a doenþa de Chagas tem sido um grande desafio, no que diz respeito O sua terapÛutica. Devido O grande dificuldade de encontrar fármacos que garantam uma aþÒo terapÛutica eficiente e menos agressora O espécie humana, diferentes produtos naturais vÛm sendo testados. Muitas espécies vegetais foram investigadas quanto O sua aþÒo leishmanicida e tripanocida na expectativa de que seus compostos metabólicos possuam atividade antiparasitária e ausÛncia ou baixa citotoxicidade. Neste estudo sobre bioatividade do a-pineno e carvacrol, avaliaram-se os potenciais leishmanicida e tripanocida. O carvacrol apresentou um percentual de inibiþÒo de 38,34% e 74,12% para as formas promastigotas e epimastigotas respectivamente, na concentraþÒo de 100Ag/mL, apresentando uma citotoxicidade de 21,62%. O a-pineno apresentou 100% e 5,30% de inibiþÒo para as formas epimastigota e promastigota na concentraþÒo de 100 Ag/mL, com citotoxicidade de 87,88%.(AU)

Leishmaniasis and Chagas Disease represent a great challenge against the modern therapeutics. Due the high difficult to find new drugs with therapeutic efficacy and low toxicity, several natural products had been screened. Many species of plants were investigated about their leishmanicidal and trypanocidal activities. Some phytocompounds are the a-pinene and carvacrol. In this work, we evaluated the bioactivities of a-pinene and carvacrol against Trypanosoma cruzi and Leishmania braziliensis cell lines. The carvacrol inhibited 38,34% and 74,12% of the promatigote and epimastigote forms, respectively at 100 Ag/mL, showing a low cytotoxic activity (21,62%). The O a-pinene inhibited 100% and 5,30% against the epimastigote and promastigote forms respectively, at 100 Ag/mL, showing a higher cytotoxic activity (87,88%).(AU)

In vitro and in vivo antileishmanial and trypanocidal studies of new N-benzene- and N-naphthalenesulfonamide derivatives.

We report in vivo and in vitro antileishmanial and trypanocidal activities of a new series of N-substituted benzene and naphthalenesulfonamides 1-15. Compounds 1-15 were screened in vitro against Leishmania infantum , Leishmania braziliensis , Leishmania guyanensis , Leishmania amazonensis , and Trypanosoma cruzi . Sulfonamides 6e, 10b, and 10d displayed remarkable activity and selectivity toward T. cruzi epimastigotes and amastigotes. 6e showed significant trypanocidal activity on parasitemia in a murine model of acute Chagas disease. Moreover, 6e, 8c, 9c, 12c, and 14d displayed interesting IC50 values against Leishmania spp promastigotes as well as L. amazonensis and L. infantum amastigotes. 9c showed excellent in vivo activity (up to 97% inhibition of the parasite growth) in a short-term treatment murine model for acute infection by L. infantum. In addition, the effect of compounds 9c and 14d on tubulin as potential target was assessed by confocal microscopy analysis applied to L. infantum promastigotes.

Phenol composition, cytotoxic and anti-kinetoplastidae activities of Lygodium venustum SW. (Lygodiaceae).

The search for new therapeutic agents has been a constant for the treatment of diseases such as leishmaniasis and Chagas disease. Most drugs used have side effects, justifying the need to evaluate the cytotoxicity of the tested products for candidates to new drugs. In this study, the bioactivity of Lygodium venustum, a cosmopolitan fern of Lygodiaceae, was assessed about their leishmanicidal and trypanocidal potential. The better activity was observed using methanol fraction, with inhibition percentage of 63% and 68% for promastigotes and epimastigotes, respectively, at a concentration of 500 µg/mL. The ethyl acetate and methanol fractions demonstrated a higher cytotoxic potential. This was the first report of leishmanicidal, trypanocidal and cytotoxic activities to L. venustum.

Evaluation of the anti-Leishmania activity of ethanol extract and fractions of the leaves from Pityrogramma calomelanos (L.) link.

Leishmaniasis is caused by parasites of the genus Leishmania. Recent reports about leishmaniasis show a few number of drugs available, indicating the necessity of new drugs. In this study, the ethanol extract and fractions of Pityrogramma calomelanos (L.) link. (Pteridaceae) were assayed to verify the cytotoxicity and in vitro leishmanicidal activity against promastigote forms of Leishmania brasiliensis. The cytotoxic assay was performed using fibroblasts NCTC929. The studies indicated a leishmanicidal effect of the ethanol extract and the ethyl-acetate fraction. However, a high cytotoxic effect was observed. The hexane and methanol fractions did not show leishmanicidal activity, nor cytotoxic effect. The phytochemical screening detected the presence of alkaloids, a class of secondary metabolites with a known leishmanicidal activity. This is the first study reporting an anti-Leishmania and cytotoxic effect of P. calomelanos, being an interesting approach in the search for drugs against this disease.

Nuclease activity and ultrastructural effects of new sulfonamides with anti-leishmanial and trypanocidal activities.

Our aim was to evaluate the in vitro efficacy of a series of N-benzenesulfonamides of amine substituted aromatic rings, sulfonamides 1-6, against Trypanosoma cruzi and Leishmania spp. and to compare their trypanocidal and leishmanicidal profile. In order to elucidate the probable mechanism of action, the interaction of selected sulfonamides with pUC18 plasmid DNA was investigated by nuclease activity assays. In addition, the cellular targets of these sulfonamides in treated parasites were also searched by transmission and scanning electron microscopy. The most active compounds 4-nitro-N-pyrimidin-2-ylbenzenesulfonamide 1a and 4-chloro-N-5-methyl-thiazol-2-yl-benzenesulfonamide 2d displayed significant in vitro activity against Leishmania spp. promastigotes, without toxicity to J774 macrophages. Selected sulfonamides 1a, 4-nitro-N-pyrazin-2-yl-benzenesulfonamide 1n and 2d were also active against Leishmania infantum intracellular amastigotes. Compounds 1n and 2d showed nuclease activity in the presence of copper salt analogous to our previous results with sulfonamide 1a. Mechanistic data reveal the involvement of a redox process. Evidence for the formation of reactive oxygen species (ROS) responsible for DNA strand scission is provided for sulfonamides 1a, 1n and 2d. Transmission electron microscopic (TEM) analysis of L. infantum promastigotes treated with compounds 1a, 1n and 2d shows an overall cellular disorganization effects which are mainly addressed to DNA bearing structures such as the nucleus, mitochondria and kinetoplast. Disruption of double nuclear membrane and loss of cellular integrity along with accumulation of cytoplasmic electrodense bodies were also frequently observed.

Anti-Trypanosoma cruzi and cytotoxic activities of Eugenia uniflora L.

Chagas disease is caused by Trypanosoma cruzi, being considered a public health problem. An alternative to combat this pathogen is the use of natural products isolated from fruits such as Eugenia uniflora, a plant used by traditional communities as food and medicine due to its antimicrobial and biological activities. Ethanolic extract from E. uniflora was used to evaluate in vitro anti-epimastigote and cytotoxic activity. This is the first record of anti-Trypanosoma activity of E. uniflora, demonstrating that a concentration presenting 50% of activity (EC(50)) was 62.76 µg/mL. Minimum inhibitory concentration (MIC) was ≤ 1024 µg/mL. Our results indicate that E. uniflora could be a source of plant-derived natural products with anti-epimastigote activity with low toxicity.

Avaliação da atividade anti-Trypanosoma e anti-Leishmania de Mentha arvensis e Turnera ulmifolia / Evaluation of the anti-Trypanosoma and anti-Leishmania activity of Mentha arvensis and Turnera ulmifolia

Tripanosomiasis or “Chagas disease”, caused by Trypanosoma cruzi, affect 10 million people in Latin America. Today, the chemotherapy is the only specific treatment against this disease, being the most used drugs the nifurtimox and benznidazole. Leishmaniasis is a disease caused by parasites of the genus Leishmania, mainly founded in regions with forests, as the Amazonia. Recent reports about the Leishmaniasis indicate a deficit of therapeutical drugs available against this disease and reinforce the necessity of the discovering of new drugs. An interesting approach against these diseases is the use of natural products, as the extracts of plants as Mentha arvensis and Turnera ulmifolia. For the in vitro assays against T. cruzi and Leishmania, was used the clone CL-B5 and promastigote forms, respectively. The cytotoxic assay was performed using fibroblasts. Our results indicated that M. arvensis was active against all strains assayed, inhibiting 65 e 47 percent of the assayed strains (IC50 = 192.3 and 531.9 ug/mL respectively), representing an interesting and alternative source of natural products with anti-kinetoplastida activity.

Doença de Chagas, causada por Trypanosoma cruzi, afeta cerca de 10 milhões de pessoas nas Américas. Atualmente, a quimioterapia é o único tratamento específico disponível para esta doença, onde os medicamentos utilizados são nifurtimox e benzonidazol. Leishmaniose tegumentar Americana no Brasil é causada por uma variedade de espécies de Leishmania e uma grande diversidade destes parasitos pode ser encontrada na Região Amazônica. Revisões recentes na quimioterapia de leishmaniose enfatizam as deficiências dos agentes terapêuticos atualmente disponíveis e mostram a necessidade urgente de novos candidatos. Uma alternativa para substituir esses medicamentos são extratos naturais de Mentha arvensis e Turnera ulmifolia. Foram preparados extratos etanólicos das folhas de M. arvensis e T. ulmifolia. Para os testes in vitro de T. cruzi, foi utilizado o clone CL-B5 e para Leishmania brasiliensis foram utilizadas formas promastigotas. O ensaio de citotoxicidade foi realizado com linhagens de fibroblastos. Nossos resultados indicam que M. arvensis foi eficaz contra as cepas de parasitos testadas apresentando 65 e 47 por cento de inibição em uma concentração de 500 ug/mL (respectivamente, CE50 = 192.3 e 531.9 ug/mL), sendo considerada uma fonte alternativa de produtos naturais com atividade contra T. cruzi e L. brasiliensis.