Bothrops jararacussu snake venom decreases CD1d, CD83, and CD86 expression on bone marrow-derived dendritic cells.

This study was designed to characterize mice bone marrow (BM) and bone marrow-derived dendritic cells (BMDC) and to compare the surface markers expression and inflammatory cytokine liberation in response to LPS and Bothrops jararacussu venom (BjV) stimulation. Typical morphology was observed in BM and BMDCs from the 4th up to the 8th day of culture using recombinant mouse GM-CSF and IL-4. A high basal level of MHC-II, CD1d, CD83, CD11c, CD80, and low CD86 was expressed by BM cells. After stimulation with GM-CSF/IL-4 for BMDCs differentiation, the BM cells differentiated into BMDCs presented MHC-II, CD1d, CD83, CD11c, CD86, and CD80 expression on the 4th - 8th day accompanied with high levels of TNF-α liberated. The difference between the surface markers' expression was observed in this time course in which CD1d, CD11c, and CD80 remained in high levels of expression, while MHC-II and CD83 showed moderate expression during the differentiation period. Also, cytokines liberation was monitored over the period of the BMDCs culture, and on the 6th day, low levels of IL-6 and IL-1ß were found, while high levels of TNF-α on the 4th and 8th days, both of which contributed to the maturity of the BMDCs. Maturation of DCs with LPS showed significant upregulation of surface markers (MHC-II, CD1d, CD83, CD86, CD80) and pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α) liberation. On the other hand, BjV induced a decrease in CD1d, CD11c, CD83, and CD86 expression in mature BMDCs which was not observed when LPS was used to stimulate BMDCs which probably induces impairment in T-cell activation.

Bothrops erythromelas venom and its action on isolated murine macrophages.

Snakebite is a universally neglected public health problem. It victimizes approximately 2.5 million people annually and kills around 125 thousand. In Brazil, the Bothrops genus is responsible for 87% of the envenoming. The species Bothrops erythromelas is endemic in the northeast region. Its venom induces local haemorrhage, coagulopathy, oedema, and necrosis and can lead to permanent disability or death. The in vitro effects of Bothrops erythromelas venom (BeV) on thioglycollate-elicited macrophages were investigated in this study. At non-cytotoxic concentrations, BeV did not interfere with the adhesion and detachment of thioglycollate-elicited macrophages. However, BeV induced lipid body formation and the activation of respiratory burst and TNF-α, but not IL-1ß and IL-6. The study aimed to extend the knowledge on the mechanism of action of BeV and its contribution toward a better characterisation of macrophage functionality under the action of Bothrops venom.

Larvicidal isoxazoles: Synthesis and their effective susceptibility towards Aedes aegypti larvae.

Twenty 3,5-disubstituted isoxazoles have been synthesized and tested against fourth instar Aedes aegypti larvae. In the synthesis of title compounds, modifications have been made in the C-5 side-chain with a view to test their larvicidal activity. These isoxazoles have been obtained by 1,3-dipolar cycloaddition of arylnitrile oxides to terminal alkynes which furnished the desired products in 20% to 79% yields. A comparative study of the larvicidal activity between 3-(3-aryl-isoxazol-5-yl)-propan-1-ols and 3-(3-aryl-isoxazol-5-yl)-propionic acids clearly demonstrated that the latter compounds possess much better larvicidal activity than the former. We also tested two esters, viz., methyl 3-[3-(phenyl)-isoxazole-5-yl] propionate and methyl 3-[3-(4-chlorophenyl)-isoxazole-5-yl] propionate, where the latter presented an excellent larvicidal profile.

Synthesis of 1,2,3-triazole derivatives and in vitro antifungal evaluation on Candida strains.

1,2,3-Triazoles have been extensively studied as compounds possessing important biological activities. In this work, we describe the synthesis of ten 2-(1-aryl-1H-1,2,3-triazol-4-yl)propan-2-ols via copper catalyzed azide alkyne cycloaddition (CuAAc or click chemistry). Next the in vitro antifungal activity of these ten compounds was evaluated using the microdilution broth method against 42 isolates of four different Candida species. Among all tested compounds, the halogen substituted triazole 2-[1-(4-chlorophenyl)-1H-(1,2,3)triazol-4-yl]propan-2-ol, revealed the best antifungal profile, showing that further modifications could be done in the structure to obtain a better drug candidate in the future.