Maturity and Fertilization Effects on Leaf Blade Tissue Percentages of Contrasting Fescue Cultivars

Palenque Plus and Ceres Torpedo are tall fescue (Festuca arundinacea Schreb.) cultivars available to the animal production systems in the humid Pampean Region of Argentina. They differ in growth cycle and morphological characteristics. At vegetative stage, Torpedo leaves are fine and tender, which suggests that their percentages of slowly digestible and indigestible tissues (SDIT) should be low. In this study we 1) explored the effects of phenological stage and nitrogen fertilization on leaf blade tissue percentages of both cultivars, using an ordination multivariate technique, and 2) evaluated the effects of these factors on the percentage of SDIT. Our results indicate that the analyzed cultivars have different histological responses to fertilization, and maturity. In vegetative stage, Torpedo responds to the fertilization increasing the percentages of live and suberizated tissues, and in reproductive stage increasing the percentage of a dead tissue which cells could be lignified. Palenque responds to both factors, maturity and fertilization increasing the percentage of sclerenchyma, but these responses interact. These different behaviours suggest that the percentage of SDIT would not be a good predictor of the quality in these cultivars in different development stages and fertilization levels

Metabolite profile of Nectandra oppositifolia Nees & Mart. and assessment of antitrypanosomal activity of bioactive compounds through efficiency analyses

EtOH extracts from the leaves and twigs of Nectandra oppositifolia Nees & Mart. shown activity against amastigote forms of Trypanosoma cruzi. These extracts were subjected to successive liquid-liquid partitioning to afford bioactive CH2Cl2 fractions. UHPLC-TOF-HRMS/MS and molecular networking were used to obtain an overview of the phytochemical composition of these active fractions. Aiming to isolate the active compounds, both CH2Cl2 fractions were subjected to fractionation using medium pressure chromatography combined with semi-preparative HPLC-UV. Using this approach, twelve compounds (1-12) were isolated and identified by NMR and HRMS analysis. Several isolated compounds displayed activity against the amastigote forms of T. cruzi, especially ethyl protocatechuate (7) with EC50 value of 18.1 μM, similar to positive control benznidazole (18.7 μM). Considering the potential of compound 7, protocatechuic acid and its respective methyl (7a), n-propyl (7b), n-butyl (7c), n-pentyl (7d), and n-hexyl (7e) esters were tested. Regarding antitrypanosomal activity, protocatechuic acid and compound 7a were inactive, while 7b-7e exhibited EC50 values from 20.4 to 11.7 μM, without cytotoxicity to mammalian cells. These results suggest that lipophilicity and molecular complexity play an important role in the activity while efficiency analysis indicates that the natural compound 7 is a promising prototype for further modifications to obtain compounds effective against the intracellular forms of T. cruzi

Chemical constituents of the volatile oil from leaves of Annona coriacea and in vitro antiprotozoal activity

The essential oil of the leaves from Annona coriacea Mart., Annonaceae, was extracted by hydrodistillation in a Clevenger apparatus and analyzed by GC/MS and GC/FID. The oil yield was 0.05% m/m. Sixty compounds were identified, in a complex mixture of sesquiterpenes (76.7%), monoterpenes (20.0%) and other constituents (3.3%). Bicyclogermacrene was its major compound (39.8%) followed by other sesquiterpenes. Most of the monoterpenes were in low concentration (<1%). Only &#946;-pinene and pseudolimonene presented the highest level of 1.6%. The volatile oil presented anti-leishmanial and trypanocidal activity against promastigotes of four species of Leishmania and trypomastigotes of Trypanosoma cruzi, showing to be more active against Leishmania (L.) chagasi (IC50 39.93 µ g/mL) (95% CI 28.00-56.95 µ g/mL)

Chemical constituents of the volatile oil from leaves of Annona coriacea and in vitro antiprotozoal activity

The essential oil of the leaves from Annona coriacea Mart., Annonaceae, was extracted by hydrodistillation in a Clevenger apparatus and analyzed by GC/MS and GC/FID. The oil yield was 0.05% m/m. Sixty compounds were identified, in a complex mixture of sesquiterpenes (76.7%), monoterpenes (20.0%) and other constituents (3.3%). Bicyclogermacrene was its major compound (39.8%) followed by other sesquiterpenes. Most of the monoterpenes were in low concentration (<1%). Only &#946;-pinene and pseudolimonene presented the highest level of 1.6%. The volatile oil presented anti-leishmanial and trypanocidal activity against promastigotes of four species of Leishmania and trypomastigotes of Trypanosoma cruzi, showing to be more active against Leishmania (L.) chagasi (IC50 39.93 µ g/mL) (95% CI 28.00-56.95 µ g/mL).21

Chemical constituents of the volatile oil from leaves of annona coriacea and in vitro antiprotozoal activity

The essential oil of the leaves from Annona coriacea Mart., Annonaceae, was extracted by hydrodistillation in a Clevenger apparatus and analyzed by GC/MS and GC/FID. The oil yield was 0.05% m/m. Sixty compounds were identified, in a complex mixture of sesquiterpenes (76.7%), monoterpenes (20.0%) and other constituents (3.3%). Bicyclogermacrene was its major compound (39.8%) followed by other sesquiterpenes. Most of the monoterpenes were in low concentration (<1%). Only β-pinene and pseudolimonene presented the highest level of 1.6%. The volatile oil presented anti-leishmanial and trypanocidal activity against promastigotes of four species of Leishmania and trypomastigotes of Trypanosoma cruzi, showing to be more active against Leishmania (L.) chagasi (IC50 39.93 µ g/mL) (95% CI 28.00-56.95 µ g/mL)2113340COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPSem informaçãoSem informaçã

In vitro antileishmanial and antitrypanosomal activities of flavanones from Baccharis retusa DC. (Asteraceae)

Leishmaniasis and Chagas' are parasitic protozoan diseases that affect the poorest population in the world, causing a high mortality and morbidity. As a result of highly toxic and long-term treatments, novel, safe and more efficacious drugs are essential. in this work, the CH2Cl2 phase from MeOH extract from the leaves of Baccharis retusa DC. (Asteraceae) was fractioned to afford two flavonoids: naringenin (1) and sakuranetin (2). These compounds were in vitro tested against Leishmania spp. promastigotes and amastigotes and Ttypanosoma cruzi trypomastigotes and amastigotes. Compound 2 presented activity against Leishmania (L) amazonensis, Leishmania (V.) braziliensis, Leishmania (L) major, and Leishmania (L) chagasi with IC50 values in the range between 43 and 52 mu g/mL and against T. cruzi trypomastigotes (IC50= 20.17 mu g/mL). Despite of the chemical similarity, compound 1 did not show antiparasitic activity. Additionally, compound 2 was subjected to a methylation procedure to give sakuranetin-4'-methyl ether (3), which resulted in an inactive compound against both Leishmania spp. and T. cnizi. the obtained results indicated that the presence of one hydroxyl group at C-4' associated to one methoxyl group at C-7 is important to the antiparasitic activity. Further drug design studies aiming derivatives could be a promising tool for the development of new therapeutic agents for Leishmaniasis and Chagas' disease. (C) 2011 Elsevier Inc. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Pesquisa e DesenvolvimentoUniversidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Diadema, SP, BrazilInst Adolfo Lutz Registro, Dept Parasitol, São Paulo, BrazilUniv Fed ABC, Ctr Ciencias Nat & Humanas, Santo Andre, SP, BrazilUniv Presbiteriana Mackenzie, Ctr Ciencias & Humanidades, São Paulo, BrazilUniversidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Diadema, SP, BrazilFAPESP: 06/57626-5FAPESP: 08/11496-9Conselho Nacional de Pesquisa e Desenvolvimento: 473405/2008-3Conselho Nacional de Pesquisa e Desenvolvimento: 477422/2009-8Web of Scienc

Activity of the antiarrhythmic drug amiodarone against Leishmania (L.) infantum: an in vitro and in vivo approach

<div><p>Abstract Background: Considering the high toxicity and limited therapies available for treating visceral leishmaniasis (VL), the drug repositioning approach represents a faster way to deliver new therapies to the market. Methods: In this study, we described for the first time the activity of a potent antiarrhythmic, amiodarone (AMD), against L. (L.)infantum and its in vitro and in vivo activity. Results: The evaluation against promastigotes has shown that amiodarone presents leishmanicidal effect against the extracellular form, with an IC50 value of 10 μM. The activity was even greater against amastigotes in comparison with promastigotes with an IC50 value of 0.5 μM. The selectivity index in relation to the intracellular form demonstrated that the antiparasitic activity was approximately 56 times higher than its toxicity to mammalian cells. Investigation of the in vivo AMD activity in the L. infantum-infected hamster model showed that 51 days after the initial infection, amiodarone was unable to reduce the parasite burden in the spleen and liver when treated for 10 consecutive days, intraperitoneally, at 50 mg/kg/day, as determined by qPCR. Although not statistically significant, AMD was able to reduce the parasite burden by 20% in the liver when treated for 10 consecutive days, orally, at 100 mg/kg/day; no reduction in the spleen was found by qPCR. Conclusions: Our findings may help further drug design studies seeking new AMD derivatives that may provide new candidates with an in vitro selectivity close to or even greater than that observed in the prototype delivering effectiveness in the experimental model of VL.</p></div

Marine alkaloids as bioactive agents against protozoal neglected tropical diseases and malaria.

Covering: 2000 up to 2021Natural products are an important resource in drug discovery, directly or indirectly delivering numerous small molecules for potential development as human medicines. Among the many classes of natural products, alkaloids have a rich history of therapeutic applications. The extensive chemodiversity of alkaloids found in the marine environment has attracted considerable attention for such uses, while the scarcity of these natural materials has stimulated efforts towards their total synthesis. This review focuses on the biological activity of marine alkaloids (covering 2000 to up to 2021) towards Neglected Tropical Diseases (NTDs) caused by protozoan parasites, and malaria. Chemotherapy represents the only form of treatment for Chagas disease, human African trypanosomiasis, leishmaniasis and malaria, but there is currently a restricted arsenal of drugs, which often elicit severe adverse effects, show variable efficacy or resistance, or are costly. Natural product scaffolds have re-emerged as a focus of academic drug discovery programmes, offering a different resource to discover new chemical entities with new modes of action. In this review, the potential of a range of marine alkaloids is analyzed, accompanied by coverage of synthetic efforts that enable further studies of key antiprotozoal natural product scaffolds