Synthesis of Esters Containing Cinnamoyl Motif with Potential Larvicide Action: A Computational, Ecotoxicity and in Vitro Cytotoxicity Assessments.

An increasing morbidity and mortality rate has been related to arboviruses transmitted by Aedes aegypti. Compounds with cinnamoyl moiety represent an alternative against mosquitos, considering their larvicidal activity. This study aimed to assess the larvicidal activity of cinnamic ester derivates against Aedes aegypti larvae, along with evaluating their toxicity effect to assess its safety as a larvicide. Ethyl cinnamate demonstrated larvicidal activity (LC50 =48.59 µg/mL). Morphological changes in larvae were detected, as a degenerative response in the thorax. Through molecular docking, the molecular binding mode between 3b, 3c, and acetylcholinesterase showed strong hydrogen bond interactions. Preliminary in vitro cell viability revealed the non-cytotoxicity of 3c. Ecotoxicity results indicated a sensitivity of Artemia salina to cinnamic esters. The phytotoxicity bioassays show potential for cinnamic compounds to enhance germination and root development. These findings suggest that compound 3c is more suitable as a larvicide since it demonstrated low toxicity.

Green Tobacco Sickness among Brazilian farm workers and genetic polymorphisms.

OBJECTIVE: Green Tobacco Sickness (GTS) is an occupational illness caused by dermal absorption of nicotine from tobacco leaves. It affects thousands of farm workers worldwide. Brazil is the second tobacco producer in the world; despite this, there are few studies on GTS among Brazilian harvesters. This study aimed to determine the prevalence of GTS among a population of tobacco workers from a producing area in northeastern Brazil and investigate whether the occurrence of the disease was influenced by factors such age, gender and smoking status. In addition, it was investigated if there was association between the onset of GTS and genetic polymorphisms in genes that encode some detoxification enzymes. A semi-structured questionnaire was used to collect demographic, behavioral and occupational data from the referred workers. Polymorphisms were tested through the Polymerase Chain Reaction technique. RESULTS: The total prevalence of GTS found was 56.9%, with a significant difference between genders (71.7% for women and 35.3% for men, p < 0.0001). No association was identified between the investigated polymorphisms and GTS. This study confirms the occurrence of GTS among tobacco harvesters in Brazil with high prevalence. The investigation suggests the need to take preventive measures to protect tobacco workers against this disease.

Preliminary in vitro evaluation of the anti-proliferative activity of guanylhydrazone derivatives.

Guanylhydrazones have shown promising antitumor activity in preclinical tumor models in several studies. In this study, we aimed at evaluating the cytotoxic effect of a series of synthetic guanylhydrazones. Different human tumor cell lines, by including HCT-8 (colon carcinoma), MDA-MB-435 (melanoma) and SF-295 (glioblastoma) were continuous exposed to guanylhydrazone derivatives for 72 hours and growth inhibition of tumor cell lines and macrophages J774 was measured using tetrazolium salt (MTT) assay. Compounds 7, 11, 16 and 17 showed strong cytotoxic activity with IC50 values lower than 10 µmol L(-1) against four tumor cell lines. Among them, 7 was less toxic to non-tumor cells. Finally, obtained data suggest that guanylhydrazones may be regarded as potential lead compounds for the design of novel anticancer agents.

Long-term exacerbation by interleukin 13 of IgE-mediated eosinophilia in rats.

Recent work shows that at least two cycles of antigen challenge applied in a 7-day interval are required to yield tissue eosinophil accumulation in IgE-passively sensitized rats. Since interleukin (IL)-13 is widely regarded as a key mediator in eosinophilic responses associated with mast cells and IgE, we investigated whether this cytokine could replace the first cycle of sensitization and challenge in its proeosinophilic role. We found that IL-13 (25 and 50 ng/cavity) injected into the rat pleural space led to eotaxin generation and a dose-dependent accumulation of eosinophils following IgE-passive sensitization and challenge 7 days later. IL-13 failed to cause eosinophil chemotaxis in vitro but induced eosinophil accumulation into the pleural cavity of naïve rats, which peaked 1 day and faded 72 h post-challenge. No changes were found 1 week after intrapleural injection of IL-13, except an approximately 40-50% increase in the number of adhered and non-adhered pleural mast cells. As recovered from the pleural effluent 1 week after IL-13, mast cells expressed the same amount of IgE bound on their surface as compared to controls. However, they generated 3-fold more LTC(4) following IgE-sensitization and challenge in vitro, keeping intact the amount of histamine released. Finally, pretreatment with zileuton (50 microg/cavity) 1 h before allergen challenge prevented eosinophil accumulation in those animals injected with IL-13 1 week before. In conclusion, our findings show that IL-13 causes a long-term exacerbation of the IgE-mediated eosinophilic response in a mechanism associated with heightened cysteinyl-leukotriene (cys-LT) production by resident mast cells.

Adoptive transfer of mast cells abolishes the inflammatory refractoriness to allergen in diabetic rats.

Mast cells are pivotal secretory cells primarily implicated in allergen-evoked inflammatory responses and are downregulated following experimental chemical diabetes. Here we tested the hypothesis that a decrease in the number and reactivity of mast cells would account for the hyporesponsiveness of diabetic rats to allergen-induced inflammation. We found that the anaphylactic release of histamine from sensitized ileum, trachea and skin tissues was clearly reduced in rats turned diabetic via intravenous administration of alloxan. Likewise, actively and passively sensitized diabetic rats mounted a weaker allergen-evoked pleural mast cell degranulation and protein extravasation, as compared to sensitized nondiabetic animals, which paralleled a marked reduction in the mast cell population in the pleural cavity. The number of mast cells enumerated in the mesentery from diabetic rats was also clearly reduced. The allergen-evoked plasma leakage in diabetic rats was restored by the transfer of mast cells from sensitized nondiabetic rats. Moreover, the adoptive transfer of sensitized mast cells from diabetics to naive animals led to a lower allergen-induced exudation as compared to the response noted after the transfer of sensitized naive mast cells. Purified mast cells from diabetic rats were hyporesponsive to antigen and compound 48/80 stimulation in vitro as attested by histamine release. Thus, our results show that the phenomenon of refractoriness of diabetic animals to allergen challenge appears to be accounted for by a reduction in the number and reactivity of mast cells.