Synthesis of 1,2,3-Triazole-Containing Methoxylated Cinnamides and Their Antileishmanial Activity against the Leishmania braziliensis Species.

Leishmaniasis is a group of infectious diseases caused by protozoan parasites that belong to the genus Leishmania. Currently, there is no human vaccine, and the available treatments are associated with toxicity, high cost, and the emergence of resistant strains. These factors highlight the need to identify new antileishmanial candidates. In this study, we synthesized twenty-four methoxylated cinnamides containing 1,2,3-triazole fragments and evaluated their antileishmanial activity against the Leishmania braziliensis species, which is the main etiological agent responsible for American Tegumentary Leishmaniasis (ATL). The cinnamides were synthetically prepared using nucleophilic acyl substitution and copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. The compounds were characterized using infrared, nuclear magnetic resonance, and high-resolution mass spectrometry techniques. We performed preliminary studies to evaluate the biological activity of these compounds against L. braziliensis promastigotes and axenic amastigotes. Compound 28, N-((1-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)-1H-1,2,3-triazole-4-yl) methyl)-3,4-dimethoxy cinnamide, demonstrated relevant antileishmanial activity with low toxicity in murine cells. The selectivity index values for this compound were superior compared with data obtained using amphotericin B. Furthermore, this cinnamide derivative reduced the infection percentage and number of recovered amastigotes in L. braziliensis-infected macrophages. It also induced an increase in reactive oxygen species production, depolarization of the mitochondrial potential, and disruption of the parasite membrane. Taken together, these findings suggest that this synthetic compound holds potential as an antileishmanial candidate and should be considered for future studies in the treatment of ATL.

Thymol as an Interesting Building Block for Promising Fungicides against Fusarium solani.

The semisynthesis of 15 new thymol derivatives was achieved through Williamson synthesis and copper-catalyzed azide-alkyne cycloaddition (CuAAC) approaches. The reaction of CuAAC using the "Click Chemistry" strategy, in the presence of an alkynyl thymol derivative and commercial or prepared azides, provided nine thymol derivatives under microwave irradiation. This procedure reduces reaction time and cost. All molecular entities were elucidated by 1H and 13C NMR, IR, and HRMS data. These derivatives were evaluated in vitro for their fungicidal activity against Fusarium solani sp. Among the nine triazolic thymol derivatives obtained, seven of them were found to have moderated antifungal activity. In contrast, naphthoquinone/thymol hybrid ether 2b displayed activity comparable with that of the commercial fungicide thiabendazole. The structure-activity relationship for the most active compound 2b was discussed, and the mode of action was predicted by a possible binding to the fungic ergosterol and interference of osmotic balance of K+ into the extracellular medium.

Synthesis of Novel Glycerol-Derived 1,2,3-Triazoles and Evaluation of Their Fungicide, Phytotoxic and Cytotoxic Activities.

The synthesis of a series of 1,2,3-triazoles using glycerol as starting material is described. The key step in the preparation of these triazolic derivatives is the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), also known as click reaction, between 4-(azidomethyl)-2,2-dimethyl-1,3-dioxolane (3) and different terminal alkynes. The eight prepared derivatives were evaluated with regard to their fungicide, phytotoxic and cytotoxic activities. The fungicidal activity was assessed in vitro against Colletotrichum gloeosporioides, the causative agent of papaya anthracnose. It was found that the compounds 1-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-1,2,3-triazol-4-yl)-cyclo-hexanol (4g) and 2-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-1,2,3-triazol-4-yl)propan-2-ol (4h) demonstrated high efficiency in controlling C. gloeosporioides when compared to the commercial fungicide tebuconazole. The triazoles did not present any phytotoxic effect when evaluated against Lactuca sativa. However, five derivatives were mitodepressive, inducing cell death detected by the presence of condensed nuclei and acted as aneugenic agents in the cell cycle of L. sativa. It is believed that glycerol derivatives bearing 1,2,3-triazole functionalities may represent a promising scaffold to be explored for the development of new agents to control C. gloeosporioides.

Ethanol extract of Cymbopogon winterianus on mortality and number of eggs of Tetranychus urticae / Extrato etanólico de Cymbopogon winterianus na mortalidade e no número de ovos de Tetranychus urticae

Plant extracts have been studied as a promising source of natural insecticides. This study assessed the effect of the ethanol extract of Cymbopogon winterianus Jowitt (citronella grass) in comparison with an insecticide containing azadirachtin (ICA) on mortality and number of eggs of Tetranychus urticae Koch (Acari: Tetranychidae) in laboratory conditions. For the tests, the mites were sprayed with the aid of a Potter spray tower. To assess the mortality of females, LC50 value for extract of citronella grass and ICA was, respectively, 2.63 and 2.83%. With respect to the number of eggs, the greatest reduction was observed at a concentration of 5% for the evaluation period of 120h, both for the extract of citronella grass (86%) and for ICA (81%). These results suggest the potential of the ethanol extract of citronella grass to control of T. urticae. However, experiments, under field conditions, involving other populations of T. urticae should be performed to verify the efficacy of this extract as an alternative to be used in pest management programs.

Extratos vegetais têm sido estudados como uma fonte promissora de inseticidas naturais. Neste trabalho, foi avaliado o efeito do extrato etanólico de Cymbopogon winterianus Jowitt (capim-citronela) em comparação com um inseticida contendo azadiractina (ICA) sobre a mortalidade e o número de ovos de Tetranychus urticae Koch (Acari: Tetranychidae), em condições de laboratório. Para a realização dos ensaios, os ácaros foram pulverizados com o auxílio da torre de Potter. Para o teste de avaliação da mortalidade de fêmeas, a CL50, para o extrato de capim-citronela e ICA, foi, respectivamente, 2,63 e 2,83%. Em relação ao número de ovos, a maior redução foi observada na concentração de 5% no intervalo de avaliação de 120h, tanto para o extrato de capim-citronela (86%) quanto para o ICA (81%). Estes resultados sugerem que o extrato etanólico de capim-citronela apresenta potencial para ser utilizado no controle de T. urticae. Entretanto, ainda devem ser realizados experimentos em condições de campo, envolvendo outras populações de T. urticae, para averiguar a eficácia deste extrato como alternativa a ser utilizada em programas de manejo da praga.

Potencial acaricida do extrato etanólico de Sapindus saponaria e de solução sabão sobre Tetranychus urticae / Acaricidal potential of ethanolic extract from Sapindus saponaria and soap solution against Tetranychus urticae

Tetranychus urticae Koch (1836) (Acari: Tetranychidae), conhecido como ácaro rajado, é uma praga que pode reduzir a produção de frutos do morangueiro em até 80%. O controle desta praga por meio de acaricidas sintéticos tem proporcionado à destruição de organismos benéficos e o desenvolvimento de populações resistentes. Como alternativa ao controle tradicional, este trabalho teve como objetivo avaliar os efeitos do extrato de Sapindus saponaria e de solução sabão sobre a oviposição e mortalidade de fêmeas de T. urticae. Os ácaros foram pulverizados, com auxílio da Torre de Potter, usando formulações do extrato/solução sabão a 1, 2, 3, 4, 5% (m/v) e avaliados em 24, 72 e 120h. Verificou-se que o extrato de S. saponaria apresentou maior eficiência (CL50, 1,18%) do que a solução sabão (CL50, 1,31%). Em relação à atividade ovicida, o maior efeito foi observado com a formulação a 5% (m/v) após 120h, tanto para o extrato de S. saponaria (60,9%) quanto para solução sabão (84%). Os resultados observados, em condições de laboratório, são favoráveis à utilização do extrato de S. saponaria e de solução sabão no controle de T. urticae em programas de manejo fitossanitário para a cultura do morango.

Tetranychus urticae Koch (1836) (Acari: Tetranychidae), known as spider mite is a pest that can reduce fruit production in strawberry up to 80%. The control of the pest by synthetic acaricides has provided the destruction of beneficial organisms and development of resistant populations. As an alternative to traditional control, this study aimed to evaluate the effects of the extract from Sapindus saponaria and soap solution on the oviposition and mortality of females of T. urticae. The mites were sprayed with the aid of a Potter Tower, using formulations of extract/soap solution at 1, 2, 3, 4, 5% (w / v) and assessed at 24, 72 and 120h. It was found that the extract efficiency (LC50, 1.18%) than the soap solution (LC50, 1.31%). Regarding the ovicidal activity, the greatest effect was observed with the formulation at 5% (w / v) after 120 hours for both the extract (60.9%) as for soap solution (84%). The results observed in laboratory conditions are favorable to the use of the extract and soap solution to control T. urticae in pest management programs for the strawberry crop.

Composição química e atividade alelopática do óleo essencial de eucalipto / Chemical composition and allelopathic activity of the eucalyptus essential oil

Os óleos essenciais constituem um tipo de metabólito secundário de grande importância econômica e estão sendo cada vez mais estudados e utilizados como potentes inibidores de sementes e do crescimento de diversas plantas. O presente trabalho teve por objetivo a análise química qualitativa e quantitativa bem como a avaliação da atividade alelopática do óleo essencial extraído das folhas frescas de eucalipto (Eucalyptus citriodora) sobre a germinação e o desenvolvimento radicular das sementes de sorgo (Sorghum bicolor L.) e pepino (Cucumis sativus L.), cultivados em placa de Petri. O óleo essencial foi obtido por hidrodestilação, utilizando um aparelho tipo Clevenger, e analisado por cromatografia em fase gasosa com detector de ionização de chama e espectrometria de massas. Foi possível identificar doze constituintes químicos correspondendo a 97,69%, com predominância dos monoterpenos oxigenados citronelal (64,92%) e iso-isopulegol (10,20%) e do citronelol (8,25%). Os ensaios biológicos utilizando o óleo essencial mostraram que o mesmo apresenta efeito alelopático, prejudicando a germinação e o desenvolvimento da radícula das sementes de sorgo e pepino, sendo a redução da germinação mais pronunciada no sorgo, e que o aumento da concentração do óleo leva a uma redução linear na capacidade germinativa e no desenvolvimento da radícula.

Essential oils consist of a type of secondary metabolite that holds great economic importance, they have been increasingly studied and used as potent inhibitors of seeds and growth of various plants. The present work aimed at the qualitative and quantitative chemical analysis and evaluation of the allelopathic activity of the essential oil extracted from fresh leaves of eucalyptus (Eucalyptus citriodora) over the germination and root development of seeds of sorghum (Sorghum bicolor L.) and cucumber (Cucumis sativus L.), grown in a Petri dish. The essential oil was obtained by steam distillation, using a Clevenger apparatus, and analyzed by chromatography in gas phase with flame ionization detector and mass spectrometry. It was possible to identify twelve chemical constituents corresponding to 97.69%, with predominance of oxygenated monoterpenes citronellal (64.92%) and iso-isopulegol (10.20%) and citronellol (8.25%). The biological essays using the essential oil showed the presence of an allelopathic effect, affecting the germination and radicule length of sorghum and cucumber seeds, the germination reduction being more pronounced in sorghum, also the increase of the oil concentration leads to a linear decrease in the germination and in the radicule length.

Cymbopogon citratus (Poaceae) essential oil on Frankliniella schultzei (Thysanoptera: Thripidae) and Myzus persicae (Hemiptera: Aphididae) / Óleo essencial de Cymbopogon citratus (Poaceae) Sobre Frankliniella schultzei (Thysanoptera: Thripidae) e Myzus persicae (Hemiptera: Aphididae)

Phytovirus vectors Frankliniella schultzei (Trybom, 1920) (Thysanoptera: Thripidae) and Myzus persicae (Sulzer, 1776) (Hemiptera: Aphididae) feed on crops of great economic importance brings large economic losses worldwide to cultivated species such as tomato and cotton. F. schultzei transmits Tospovirus, Groundnut ring spot virus (GRSV) and Tomato spotted wilt virus (TSWV) to tomato plants and M. persicae transmits Potato virus Y (PVY), Tomato yellow top virus (ToYTV) and Tomato bottom yellow leaf virus (TBYLV) to tomato crops. Chemical constituents of essential oils have been increasingly studied because they present a wide range of biological activities. The aim of this work was to characterize Cymbopogon citratus essential oil and evaluate its potential insecticide activity against F. schultzei and M. persicae. The essential oil was obtained from fresh leaves by hydrodistillation using a Clevenger apparatus. Its yield (1.04%) was determined relative to the dry mass of the plant. Qualitative analysis was performed by gas chromatography coupled to mass spectrometry and chemical constituent content was determined by gas chromatography with a flame ionization detector. Nine compounds were identified, with geranial (49.98%) and neral (37.78%) being the major components. The insects were sprayed with C. citratus essential oil at different concentrations using a Potter tower. The LC50 values for M. persicae and F. schultzei were 0.28% and 1.49%, respectively. Essential oil from C. citratus is a promising natural alternative for developing pesticides to manage M. persicae.

Os vetores de fitovírus Frankliniella schultzei (Trybom, 1920) (Thysanoptera: Thripidae) e Myzus persicae (Sulzer, 1776) (Hemiptera: Aphididae) se alimentam de culturas de grande importância econômica, trazendo grandes perdas econômicas em todo o mundo para as espécies cultivadas, como tomate e algodão. F. schultzei transmite Tospovirus, Groundnut ring spot virus (GRSV) e Tomato spotted wilt virus (TSWV) em tomateiro and M. persicae transmite Potato virus Y (PVY), Tomato yellow top virus (ToYTV) e Tomato bottom yellow leaf virus (TBYLV) ao tomateiro. Os constituintes químicos dos óleos essenciais têm sido cada vez mais estudados, pois apresentam uma ampla gama de atividades biológicas. O objetivo deste trabalho foi caracterizar o óleo essencial de Cymbopogon citratus e avaliar o seu potencial inseticida sobre F. schultzei e M. persicae. O óleo essencial foi obtido a partir de folhas frescas por hidrodestilação utilizando um aparelho Clevenger. O seu rendimento (1,04%) foi determinado em relação à massa seca da planta. A análise qualitativa foi realizada por cromatografia gasosa acoplada a espectrometria de massa e o teor dos constituintes químicos foi determinado por cromatografia gasosa com detector de ionização de chama. Nove compostos foram identificados, com geranial (49,98%) e neral (37,78%), sendo os componentes principais. Os insetos foram pulverizados com óleo essencial de C. citratus em diferentes concentrações utilizando uma torre de Potter. Os valores de CL50 de M. persicae e F. schultzei foram de 0,28% e 1,49%, respectivamente. Óleo essencial de C. citratus é uma alternativa natural promissor para o desenvolvimento de inseticidas para o manejo de M. persicae.