Identification of novel Zika virus NS3 protease inhibitors with different inhibition modes by integrative experimental and computational approaches.

Zika virus (ZIKV) infection is associated with severe neurological disorders and congenital malformation. Despite efforts to eradicate the disease, there is still neither vaccine nor approved drugs to treat ZIKV infection. The NS2B-NS3 protease is a validated drug target since it is essential to polyprotein virus maturation. In the present study, we describe an experimental screening of 2,320 compounds from the chemical library of the Muséum National d'Histoire Naturelle of Paris on ZIKV NS2B-NS3 protease. A total of 96 hits were identified with 90% or more of inhibitory activity at 10 µM. Amongst the most active compounds, five were analyzed for their inhibitory mechanisms by kinetics assays and computational approaches such as molecular docking. 2-(3-methoxyphenoxy) benzoic acid (compound 945) show characteristics of a competitive inhibition (Ki = 0.49 µM) that was corroborated by its molecular docking at the active site of the NS2B-NS3 protease. Taxifolin (compound 2292) behaves as an allosteric inhibitor whereas 3,8,9-trihydroxy-2-methyl-1H-phenalen-1-one (compound 128), harmol (compound 368) and anthrapurpurin (compound 1499) show uncompetitive inhibitions. These new NS2B-NS3 protease inhibitors are valuable hits to further hit-to-lead optimization.

Hypoglycemic and Antihyperlipidemic effects of Syzygium cumini (Lamarck) Skeels and Syzygiumpaniculatum (Gaertn.)

SUMMARY Introduction: there is a recent increase in interest in the use of medicinal and phytotherapeutic plants. Objective: to verify the effect of ethanolic extracts from different parts of fruits of two species of the genus Syzygium, on glucose and lipid levels in the blood, using animal models. Results: the bark extract of the seeds of S. cumini (Lamarck) Skeels proved to be effective in reducing blood glucose levels. This same extract was also effective in lowering blood cholesterol levels. The extract from the seed nuclei of S. cumini (Lamarck) Skeels and S. paniculatum (Gaertn) were effective in reducing blood triglyceride levels. Extracts from all parts of the fruits of S. cumini (Lamarck) Skeels and of the seed nuclei of S. panic-ulatum (Gaertn) prevented weight gain in the animals. Conclusión: in general, the seed extract of both species showed a direct influence on the parameters and characteristics under study.

Introducción: hay un reciente aumento del interés en el uso de plantas medicinales y fitoterapéuticas. Objetivo: verificar el efecto de los extractos etanólicos de diferentes partes de frutos de dos especies del género Syzygium, sobre los niveles de glucosa y lípidos en la sangre, utilizando modelos animales. Resultados: el extracto de corteza de las semillas de S. cumini (Lamarck) Skeels demostró ser eficaz para reducir los niveles de glucosa en la sangre. Este mismo extracto también fue eficaz para reducir los niveles de colesterol en la sangre. El extracto de los núcleos de semillas de S. cumini (Lamarck) Skeels y S. paniculatum (Gaertn) fueron eficaces para reducir los niveles de triglicéridos en la sangre. Los extractos de todas las partes de los frutos de S. cumini (Lamarck) Skeels y de los núcleos de semillas de S. paniculatum (Gaertn) impidieron el aumento de peso en los animales. Conclusión: en general, el extracto de semillas de ambas especies mostró una influencia directa sobre los parámetros y características en estudio.

Introdução: há um aumento recente do interesse pelo uso de plantas medicinais e fitoterápicas. Objetivo: verificar o efeito de extratos etanólicos de diferentes partes de frutos de duas espécies do gênero Syzygium, sobre os níveis de glicose e lipídios no sangue, por meio de modelos animais. Resultados: o extrato da casca das sementes de S. cumini (Lamarck) Skeels mostrou-se eficaz na redução da glicemia. Este mesmo extrato também foi eficaz na redução dos níveis de colesterol no sangue. Os extratos dos núcleos das sementes de S. cumini (Lamarck) Skeels e S. paniculatum (Gaertn) foram eficazes na redução dos níveis de triglicerídeos no sangue. Extratos de todas as partes dos frutos de S. cumini (Lamarck) Skeels e dos núcleos das sementes de S. pani-culatum (Gaertn) impediram o ganho de peso nos animais. Conclusão: em geral, o extrato de sementes de ambas as espécies apresentou influência direta nos parâmetros e características em estudo.

Liposomes Composed by Membrane Lipid Extracts from Macrophage Cell Line as a Delivery of the Trypanocidal N,N'-Squaramide 17 towards Trypanosoma cruzi.

Chagas is a neglected tropical disease caused by Trypanosoma cruzi, and affects about 25 million people worldwide. N, N'-Squaramide 17 (S) is a trypanocidal compound with relevant in vivo effectiveness. Here, we produced, characterized, and evaluated cytotoxic and trypanocidal effects of macrophage-mimetic liposomes from lipids extracted of RAW 264.7 cells to release S. As results, the average hydrodynamic diameter and Zeta potential of mimetic lipid membranes containing S (MLS) was 196.5 ± 11 nm and -61.43 ± 2.3 mV, respectively. Drug entrapment efficiency was 73.35% ± 2.05%. After a 72 h treatment, MLS was observed to be active against epimastigotes in vitro (IC50 = 15.85 ± 4.82 µM) and intracellular amastigotes (IC50 = 24.92 ± 4.80 µM). Also, it induced low cytotoxicity with CC50 of 1199.50 ± 1.22 µM towards VERO cells and of 1973.97 ± 5.98 µM in RAW 264.7. MLS also induced fissures in parasite membrane with a diameter of approximately 200 nm in epimastigotes. MLS showed low cytotoxicity in mammalian cells and high trypanocidal activity revealing this nanostructure a promising candidate for the development of Chagas disease treatment.

Larvicidal and pupicidal activities of eco-friendly phenolic lipid products from Anacardium occidentale nutshell against arbovirus vectors.

Aedes aegypti and Culex quinquefasciatus are vectors of diseases that constitute public health problems. The discovery of products capable of inhibiting their development which are less harmful to the environment would have a huge impact on vector control. Here, natural cashew nut shell liquid (CNSL), technical CNSL, anacardic acid, cardanol, and cardol were isolated from Anacardium occidentale and evaluated for larvicidal and pupicidal activity against Ae. aegypti and Cx. quinquefasciatus under laboratory and field conditions. The activities of phenol, resorcinol, salicylic acid, and pentadecane, commercial chemicals similar in structure to nut shell derivatives, were also evaluated. All of the fractions extracted from A. occidentale oil exerted larvicidal effects against both mosquito species (LC50 5.4-22.6 mg/L), and two of the aforementioned were effective against pupae (LC50 90.8-109.7 mg/L). Of all the fractions tested, cardol demonstrated the strongest larvicidal and pupicidal effects and presented the most prolonged residual activity against the larvae and pupae of Ae. aegypti and Cx. quinquefasciatus under field conditions. This study suggests that A. occidentale nut shell derivatives are sustainable and promising candidates for the development of novel insecticides to overcome the problem of harmful chemical insecticides.

Anticancer Properties of Essential Oils: An Overview.

BACKGROUND: Essential oils are complex mixtures of low molecular weight compounds extracted from plants. Their main constituents are terpenes and phenylpropanoids, which are responsible for their biological and pharmaceutical properties, such as insecticidal, parasiticidal, antimicrobial, antioxidant, anti-inflammatory, analgesic, antinociceptive, anticarcinogenic, and antitumor properties. Cancer is a complex genetic disease considered as a serious public health problem worldwide, accounting for more than 8 million deaths annually. OBJECTIVE: The activities of prevention and treatment of different types of cancer and the medicinal potential of essential oils are addressed in this review. CONCLUSION: Several studies have demonstrated anti-carcinogenic and antitumor activity for many essential oils obtained from various plant species. They may be used as a substitution to or in addition to conventional anti-cancer therapy. Although many studies report possible mechanisms of action for essential oils compounds, more studies are necessary in order to apply them safely and appropriately in cancer therapy.

Essential oils: in vitro activity against Leishmania amazonensis, cytotoxicity and chemical composition.

BACKGROUND: The current chemotherapy for cutaneous leishmaniosis (CL) has a series of drug limitations such as toxic side effects, long duration, high costs and drug resistance, which requires the development of new drugs or effective alternatives to the CL treatment. Essential oils (EOs) are complex mixtures of secondary metabolites from various plants. It has been shown that several EOs, or their constituents, have inhibitory activity against protozoa. Thus, this study aims to evaluate the biological activity of different essential oils (EOs) on Leishmania (L.) amazonensis promastigotes forms, as well as their cytotoxicity on mammalian cells and chemical composition. METHODS: Sixteen EOs were evaluated by mean of IC50/24 h and cytotoxicity against L6 cells (CC50/24 h) using Resazurin assay. Only those EOs that presented better results for IC50/24 h were submitted to GC-MS analysis to determine their chemical constitution. RESULTS: The EO from Cinnamodendron dinisii, Matricaria chamomilla, Myroxylon peruiferum, Salvia sclarea, Bulnesia sarmientoi, Ferula galbaniflua, Siparuna guianensis and Melissa officinalis were the most active against L. amazonensis with IC50/24 h ranging from 54.05 to 162.25 µg/mL. Analysis of EOs by GC-MS showed mainly the presence of ß-farnesene (52.73 %) and bisabolol oxide (12.09 %) for M. chamomilla; α-copaene (13.41 %), safrole (8.35 %) and δ-cadinene (7.08 %) for M. peruiferum; linalool (28.80 %) and linalyl acetate (60.08 %) for S. sclarea; guaiol (48.29 %) and 2-undecanone (19.49 %) for B. sarmientoi; ethyl phthalate (13.09 %) and methyl-8-pimaren-18-oate (41.82 %) for F. galbaniflua; and neral (37.18 %) and citral (5.02 %) for M. officinalis. CONCLUSION: The EO from F. galbaniflua showed to be effective against L. amazonensis promastigotes forms and presented low cytotoxic activity against L6 cells. Thus, it represents a strong candidate for future studies aiming its molecular activity on these pathogenic parasites.

Biological activity of the essential oils from Cinnamodendron dinisii and Siparuna guianensis.

This study had analyzed the antibacterial, antifungal and trypanocidal activity of the essential oils from Cinnamodendron dinisii Schwacke (Canellaceae) and Siparuna guianensis Aublet (Siparunaceae). The essential oils were obtained from fresh leaves by hydrodistillation, using a modified Clevenger apparatus. Chemical analysis by gas-liquid chromatography coupled to mass spectrometry (GC-MS) showed that these essential oils are rich in monoterpene and sesquiterpene hydrocarbons. Activity against the pathogenic bacteria Escherichia coli , Listeria monocytogenes , Pseudomonas aeruginosa , Salmonella choleraesuis and Staphylococcus aureus was evaluated with the agar cavity diffusion method, while activity on the filamentous fungi Aspergillus flavus , Aspergillus niger , Aspergillus carbonarius and Penicillium commune was evaluated by the disk diffusion technique. Trypanocidal activity was tested against Trypanosoma cruzi epimastigotes, using the Tetrazolium salt (MTT) colorimetric assay. Both essential oils exhibited low inhibitory effect towards bacteria, showing high MIC values (125-500 µg mL (-1) ), with Gram positive bacteria being more susceptible. Better inhibitory effect was obtained for the evaluated fungi, with lower MIC values (7.81-250 µg mL (-1) ), being A. flavus the most susceptible species. Both essential oils presented low trypanocidal activity, with IC 50 /24 h values of 209.30 µg mL (-1) for S. guianensis and 282.93 µg mL (-1) for C. dinisii . Thus, the high values observed for the MIC of evaluated bacteria and for IC 50 /24 h of T. cruzi , suggest that the essential oils have a low inhibitory activity against these microorganisms. In addition, the low MIC values observed for the tested fungi species indicate good inhibitory activity on these microorganisms's growth.

Biological activity of the essential oils from Cinnamodendron dinisii and Siparuna guianensis

This study had analyzed the antibacterial, antifungal and trypanocidal activity of the essential oils from Cinnamodendron dinisii Schwacke (Canellaceae) and Siparuna guianensis Aublet (Siparunaceae). The essential oils were obtained from fresh leaves by hydrodistillation, using a modified Clevenger apparatus. Chemical analysis by gas-liquid chromatography coupled to mass spectrometry (GC-MS) showed that these essential oils are rich in monoterpene and sesquiterpene hydrocarbons. Activity against the pathogenic bacteria Escherichia coli, Listeria monocytogenes, Pseudomonas aeruginosa, Salmonella choleraesuis and Staphylococcus aureus was evaluated with the agar cavity diffusion method, while activity on the filamentous fungi Aspergillus flavus, Aspergillus niger, Aspergillus carbonarius and Penicillium commune was evaluated by the disk diffusion technique. Trypanocidal activity was tested against Trypanosoma cruzi epimastigotes, using the Tetrazolium salt (MTT) colorimetric assay. Both essential oils exhibited low inhibitory effect towards bacteria, showing high MIC values (125–500 μg mL−1), with Gram positive bacteria being more susceptible. Better inhibitory effect was obtained for the evaluated fungi, with lower MIC values (7.81–250 μg mL−1), being A. flavus the most susceptible species. Both essential oils presented low trypanocidal activity, with IC50/24 h values of 209.30 μg mL−1 for S. guianensis and 282.93 μg mL−1 for C. dinisii. Thus, the high values observed for the MIC of evaluated bacteria and for IC50/24 h of T. cruzi, suggest that the essential oils have a low inhibitory activity against these microorganisms. In addition, the low MIC values observed for the tested fungi species indicate good inhibitory activity on these microorganisms’s growth.

Chemical Composition and Antioxidant Activity of Essential Oils from Cinnamodendron dinisii Schwacke and Siparuna guianensis Aublet.

The objectives of this study were to chemically characterize and evaluate the antioxidant activity of essential oils Cinnamodendron dinisii Schwacke (pepper) and Siparuna guianensis Aublet (negramina). The essential oil was isolated by hydrodistillation using a Clevenger modified apparatus, and the identification and quantification of constituents, through GC/MS and GC-FID analysis. The antioxidant activity was evaluated using ß-carotene/linoleic acid system and the DPPH radical sequestering method. In chromatographic analysis, the majority constituents found in the essential oil of C. dinisii were bicyclic monoterpenes, α-pinene (35.41%), ß-pinene (17.81%), sabinene (12.01%) and sesquiterpene bicyclogermacrene (7.59%). In the essential oil of the fresh leaves of Siparuna guianensis Aublet, acyclic monoterpene, ß-myrcene (13.14%), and sesquiterpenes, germacrene-D (8.68%) and bicyclogermacrene (16.71%) were identified. The antioxidant activity was low by the ß-carotene/linoleic acid test and was not evidenced by the DPPH test, for both oils evaluated.

Caracterização química e anatômica de folhas de tomilho provenientes de plantas submetidas a diferentes condições luminosas / Characterization chemical and anatomical thyme leaves from plants subjected to different lighting conditions

Várias espécies de plantas possuem capacidade de desenvolver folhas com anatomias distintas quando cultivadas em diferentes condições de luz, as quais influenciam diretamente o crescimento e o desenvolvimento das mesmas, causando alterações morfofisiológicas. Diante da falta de informação a respeito de como o fator ambiental interfere sobre a fisiologia do desenvolvimento e do metabolismo das plantas de Thymus vulgaris, este trabalho objetivou estudar os efeitos das intensidades luminosas de 100, 50 e 30%, na produção e no teor de timol de seu óleo essencial, em sua anatomia foliar e na produtividade de biomassa fresca. Maiores rendimentos de óleo essencial foram encontrados para os níveis de irradiância de 100 e 50%. Para as análises anatômicas observa-se que quanto maior o índice de irradiância maiores espessura do limbo foliar, do mesofilo e das faces adaxial e abaxial são alcançadas, resultando maior produção de biomassa fresca.

Several plant species are capable of developing leaves with distinct anatomies when grown under different light conditions, which directly influence their growth and development and cause morphophysiological changes. Given the lack of information about how the environmental factors interfere with the physiology of development and metabolism of Thymus vulgaris plants, this study investigated the effects of light intensities of 100, 50 and 30% on the production and thymol content of the essential oil, on their leaf anatomy and on the productivity of fresh biomass. Higher yields of oil were found for levels of irradiance of 100 and 50%. Greater leaf, mesophyll and adaxial and abaxial thicknesses were achieved with a higher irradiance index, resulting in a higher production of fresh biomass.

Controle microbiológico de alimentos utilizando óleo essencial de Pimpinella anisum (erva-doce) / Food microbiological control using essential oil of Pimpinella anisum

O consumo de produtos naturais que substituam aditivos químicos tem sido uma opção para aqueles que procuram hábitos saudáveis e segurança alimentar. Os condimentos possuem comprovada atividade biológica sobre fungos e bactérias. Por isso, sempre foram utilizados como conservantes de alimentos. Este trabalho foi realizado com o objetivo de avaliar o efeito “in vitro” do óleo essencial de erva-doce (Pimpinella anisum), sobre as bactérias Staphylococcus aureus e Escherichia coli e sobre os fungos Aspergillus flavus e Aspergillus parasiticus. O óleo essencial foi extraído pela técnica hidrodestilação utilizando aparelho de Clevenger modificado e testado nas concentrações de 50; 40; 30; 20; 10; 5; 1; 0,5 e 0.1% para as bactérias e nas concentrações de 2; 1; 0,5; 0;25 e 0,1 µL/mL para fungos. O óleo apresentou uma elevada atividade bacteriana com uma concentração mínima inibitória (CMI) de 1% para a E.coli, porém não apresentou atividade frente a S. aureus. Os valores de CMI encontrados para o A. flavus e A. parasiticus foram de 0,5 e 2 µL/mL, respectivamente. Verificou-se que o óleo essencial apresentou efeito inibitório sobre os micro-organismos estudados, sendo, portanto, uma alternativa no controle microbiológico de alimentos.

Composition of the essential oil from the leaves of tree domestic varieties and one wild variety of the guava plant (Psidium guajava L., Myrtaceae) / Avaliação dos constituintes dos óleos essenciais de folhas de goiabeira (Psidium guajava L., Myrtaceae) de três cultivares e da planta silvestre

The compositions of the essential oils from the leaves of three domestic varieties of the guava tree Psidium guajava L. (Paluma, Século XXI and Pedro Sato) and of one wild variety were compared. Essential oils were extracted by steam distillation, the components were identified by gas chromatography coupled to mass spectrometry GC-MS, and the apparent concentrations were determined by gas chromatography with a flame ionization detector. The results demonstrated that the three essential oils contained many common substances with a prevalence of 1,8-cineole, whereas the essential oil of the Paluma variety contained 1,8-cineole (42.68 percent) as the major constituent, as well as α-terpineol (38.68 percent). The principal components of the essential oil of the Século XXI variety were 1,8-cineole (18.83 percent), trans-caryophyllene (12.08 percent), and selin-11-en-4-αol (20.98 percent), while those of the Pedro Sato variety and of the wild plant were 1,8-cineole (17.68 percent) and (12.83 percent), caryophyllene oxide (9.34 percent) and (9.09 percent), and selin-11-en-4-α-ol (21.46 percent) and (22.19 percent), respectively.

Os óleos essenciais de folhas de goiabeira Psidium guajava L. de três diferentes cultivares (Paluma, Século XXI e Pedro Sato) e da planta silvestre foram analisados a fim de comparar os seus constituintes. O óleo essencial foi obtido por hidrodestilação em aparelho de Clevenger modificado. Para a caracterização e quantificação dos compostos presentes por CG-EM e CG respectivamente. Os resultados mostraram que os três óleos essenciais analisados apresentam inúmeras substâncias em comum com a predominância do 1,8-cineol. O óleo essencial da cultivar Paluma se difere dos demais devido a alta concentração de 1,8-cineol (42,68 por cento) e do α-terpineol (38,68 por cento). No óleo essencial da cultivar Século XXI observase a presença do 1,8 cineol (18,83 por cento), trans-carifileno (12,08 por cento) e o selin-11-en-4-α-ol (20,98 por cento) como majoritários, enquanto que a cultivar Pedro Sato e a planta silvestre apresentaram com o 1,8 cineol com (17,68 por cento) e (12,83 por cento), oxido de cariofileno (9,34 por cento) e (9,09 por cento) e o selin-11-en-4-α-ol com (21,46 por cento) e (22,19 por cento), respectivamente.