Persea americana Mill.: Evaluation of cytogenotoxicity and phytochemical prospection of leaf extracts

Abstract Persea americana Mill., belonging to the family Lauraceae, is noteworthy for the large amount of ethnopharmacological information in its regard, attributing to it many and varied medicinal properties. The tea and alcoholic extracts made from its leaves are used in folk medicine to treat various ailments. This study was designed to analyze the cytogenotoxicity and underlying chemistry of aqueous and hydroalcoholic extracts of avocado leaves, using the Allium cepa and micronucleus tests. The results obtained by applying the experimental models demonstrate that the extracts did not have a genotoxic effect at any of the concentrations analyzed, and even demonstrated a certain protective effect, possibly due to the presence of flavonoids and phenols, both of which are antioxidant substances. However, the extracts did present a cytotoxic effect. There were numerous karyorrhectic cells and those with nuclear alterations related to cell death. At the highest concentrations, it was possible to observe cytoplasmic alterations and binucleated cells. The extracts also caused a significant reduction in the number of cells undergoing division. These effects can be a response to the phytochemical agents present in the extracts. The results suggest that the extracts contain bioactive components that deserve further studies related to cancer therapies.

Metabolic characterization and oil profile of sunflower cultivars cultivated with increasing nitrogen doses / Caracterização metabólica e perfil do óleo de cultivares de girassol cultivados sob doses crescentes de nitrogênio

Sunflower (Helianthus annuus L.) has great economic importance due to its oil yield and quality. Among the factors influencing these parameters, nitrogen fertilization stands out. In this study we evaluated the effect of different N-urea doses (0,10,30,50,90,130 kg N-urea ha-1) at planting and 30 days after emergency on soluble fractions, oil profile and yield of three sunflower cultivars (BRS324, Catissol 01and Neon). Plants were harvested at the flowering stage for metabolic study, and at the end of the cycle for oil extraction and characterization. The Catissol 01 genotype presented the highest N-NO3- accumulation capacity, mainly in the stem. The Neon genotype presented the highest achene production at 30 and 50 kg N ha-1. Oleic oil had the highest yield, with the Catissol 01 and Neon cultivar standing out. Among the cultivars, Catissol 01 is economically more suitable for biofuel production, when cultivated at 50 kg N ha-1 since higher N doses did not result in increased oil yield.

O girassol é uma espécie com importante valor econômico pela qualidade e rendimento de óleo. Entre os fatores que influenciam esses parâmetros se destaca a fertilização nitrogenada. Este trabalho avaliou o efeito de doses crescentes de N-uréia (0, 10, 30, 50, 90, 130 kg de N-Uréia ha-1 aplicadas no plantio e aos 30 dias após a emergência) sobre as frações solúveis, rendimento e perfil do óleo de três genótipos de girassol (BRS324, Neon e Catissol 01). As plantas foram coletadas no estádio de floração para o estudo metabólico e ao final do ciclo para a extração e caracterização de óleo. O genótipo Catissol 01 apresentou maior capacidade de acúmulo de N-NO3-, preferencialmente no caule. A maior produção de óleo por planta foi observada no BRS324, nas doses entre 30 e 50 kg N ha-1, embora o genótipo Neon tenha apresentado a maior produção de aquênios. O ácido oléico foi o de maior rendimento com destaque para os genótipos Catissol 01 e Neon. Dentre os genótipos avaliados, o Catissol 01 é economicamente mais indicado para a produção de óleo destinada ao biocombustível, quando cultivado com a dose de 50 kg N ha-1, pois doses superiores de N não resultam em aumento na produção de óleo.

Grain production fatty acid and oil profile from sunflower cultivars receiving different boron doses / Produção de grãos, perfil de óleo e ácido graxo em cultivares de girassol submetidos a diferentes doses de boro

Among the main factors that affect the productivity of crops is deficiency of nutrients. Boron (B) is an essential micronutrient for plants, and sunflower is one of the most sensitive plants to deficiency of the element. Its inadequate supply can impair sunflower plants' metabolism and grain and oil yield. The objective of this study was to assess the effect of different boron doses on the production of sunflower grains and the content and quality of the oil obtained from them. The experimental design was randomized blocks in a factorial scheme with three cultivars (Helio251, BRS323, BRS324) and four B doses (0, 2.5, 5.0, 8.0 kg ha-1). Two harvests were performed, the first in the R5 reproductive stage and the second at the end of the R9 cycle. In both cases, the levels of B in the capitulum were measured. At the end of the cycle, the grain yield, crude protein and oil content in the grains and fatty acid profile were analyzed. The cultivars responded differently to the treatments with B. The boron fertilization influenced the grain yield and oil content, but was not correlated with the profile of the majority unsaturated fatty acids and crude protein in the grains. Variations were observed in the fatty acid profile between the cultivars, an important aspect that needs to be evaluated according to the purpose of the production. In soil with lower availability of B, cultivar BRS323 was most efficient in B uptake, grain yield and oil content and quality.

Dentre os principais fatores que afetam a produtividade das culturas está a deficiência de nutrientes. O Boro (B) é um micronutriente essencial para plantas, e o girassol é uma das mais sensíveis à deficiência desse elemento. Seu fornecimento inadequado pode prejudicar o metabolismo, a produção de óleo e grãos das plantas de girassol. O objetivo deste estudo foi avaliar o efeito de diferentes doses de boro na produção de grãos, conteúdo a qualidade do óleo de girassol. O experimento foi conduzido em delineamento de blocos ao acaso em esquema fatorial com três cultivares (Helio251, BRS323, BRS324) e quatro doses de B (0; 2,5; 5,0; 8,0 kg ha-1). Foram realizadas duas coletas, a primeira na fase reprodutiva R5 e a segunda no final do ciclo R9. Em ambos os casos, os níveis de B no capítulo foram medidos. No final do ciclo, foram analisados a produção de grãos, teor de proteína bruta e óleo nos grãos e perfil de ácidos graxos. Os cultivares responderam diferentemente aos tratamentos com B. A adubação com boro influenciou o rendimento de grãos e teor de óleo, mas não se correlacionou com o perfil da maioria dos ácidos graxos insaturados e da proteína bruta nos grãos. Foram observadas variações no perfil de ácidos graxos entre cultivares, um aspecto importante que precisa ser avaliado de acordo com a finalidade da produção. No solo com menor disponibilidade de B, o cultivar BRS323 foi mais eficiente na absorção de B, rendimento de grãos, teor e qualidade de óleo.

Synthesis and molecular modelling studies of pyrimidinones and pyrrolo[34-d]-pyrimidinodiones as new antiplasmodial compounds

BACKGROUND Malaria is responsible for 429,000 deaths per year worldwide, and more than 200 million cases were reported in 2015. Increasing parasite resistance has imposed restrictions to the currently available antimalarial drugs. Thus, the search for new, effective and safe antimalarial drugs is crucial. Heterocyclic compounds, such as dihydropyrimidinones (DHPM), synthesised via the Biginelli multicomponent reaction, as well as bicyclic compounds synthesised from DHPMs, have emerged as potential antimalarial candidates in the last few years. METHODS Thirty compounds were synthesised employing the Biginelli multicomponent reaction and subsequent one-pot substitution/cyclisation protocol; the compounds were then evaluated in vitro against chloroquine-resistant Plasmodium falciparum parasites (W2 strain). Drug cytotoxicity in baseline kidney African Green Monkey cells (BGM) was also evaluated. The most active in vitro compounds were evaluated against P. berghei parasites in mice. Additionally, we performed an in silico target fishing approach with the most active compounds, aiming to shed some light into the mechanism at a molecular level. RESULTS The synthetic route chosen was effective, leading to products with high purity and yields ranging from 10-84%. Three out of the 30 compounds tested were identified as active against the parasite and presented low toxicity. The in silico study suggested that among all the molecular targets identified by our target fishing approach, Protein Kinase 3 (PK5) and Glycogen Synthase Kinase 3β (GSK-3β) are the most likely molecular targets for the synthesised compounds. CONCLUSIONS We were able to easily obtain a collection of heterocyclic compounds with in vitro anti-P. falciparum activity that can be used as scaffolds for the design and development of new antiplasmodial drugs.

Alterations in the oxidative metabolism of Rhipicephalus (Boophilus) microplus ticks in response to exposure to the insect growth regulator fluazuron / Alterações no metabolismo oxidativo de carrapatos Rhipicephalus (Boophilus) microplus em resposta à exposição ao regulador de crescimento fluazuron

Abstract Aiming to characterize the potential off-target effects of fluazuron on ticks, biochemical analyses were conducted to evaluate changes in the carbohydrate metabolism of Rhipicephalus (Boophilus) microplus ticks after exposure to fluazuron. Hemolymph and fat body were collected from female ticks before and after (4, 8 and 15 days) exposure to fluazuron. Spectrophotometric analyses were done to quantify glucose concentration and lactate dehydrogenase (LDH) activity in the hemolymph and the concentration of glycogen in the tick’s fat body. High Performance Liquid Chromatography (HPLC) was employed to determine the concentration of carboxylic acids in the hemolymph and to evaluate changes in intermediary metabolic processes requiring oxygen consumption. Increases in the levels of LDH activity and lactic acid concentration indicated that fluazuron enhanced fermentative metabolism in ticks. Exposure to fluazuron was also found to increase glucose concentrations in the hemolymph over time, although no significant differences were noted daily. In addition to expanding the body of knowledge about the mode of action of fluazuron, investigations into these mechanisms may also be useful in discovering new and as yet unexplored secondary effects.

Resumo Com o objetivo de caracterizar os efeitos não-alvo da ação do fluazuron, foram realizados testes bioquímicos para analisar possíveis alterações no metabolismo de carboidratos em carrapatos Rhipicephalus (Boophilus) microplus após sua exposição ao composto. Foram coletados hemolinfa e corpo gorduroso de fêmeas ingurgitadas antes e após (4, 8 e 15 dias) a exposição ao fluazuron. Análises espectrofotométricas foram usadas para quantificar a concentração de glicose e a atividade da lactato desidrogenase (LDH) na hemolinfa e concentração de glicogênio no corpo gorduroso. Cromatografia Líquida de Alta Eficiência (CLAE) foi usada para determinação das concentrações de ácidos carboxílicos na hemolinfa e avaliar possíveis alterações em metabolismo intermediário em relação ao consumo de oxigênio. Aumento na atividade de LDH e concentração de ácido lático indicaram que o fluazuron pode regular o metabolismo fermentativo em carrapatos. A exposição ao fluazuron também aumentou a concentração de glicose na hemolinfa, apesar de não ter havido diferença significativa na comparação entre as médias no mesmo dia de avaliação. Além de aumentar o conhecimento sobre o modo de ação do fluazuron, investigações sobre tais mecanismos também são úteis no descobrimento de novos efeitos secundários ainda não explorados.