Role of brain extracellular vesicles in air pollution-related cognitive impairment and neurodegeneration.

A relationship between environmental exposure to air pollution and cognitive impairment and neurological disorders has been described. Previous literature has focused on the direct effects of the air pollution components on neuronal and glial cells, as well as on involvement of oxidative stress and neuroinflammation on microglia and astrocyte reactivity. However, other mechanisms involved in the air pollution effects on central nervous system (CNS) toxicity can be playing critical roles. Increasingly, extracellular vesicle's (EVs) mediated intercellular communication is being recognized as impacting the development of cognitive impairment and neurological disorders like Alzheimer's disease and others. Here we describe the available evidence about toxic air pollutants and its components on brain, an involvement of brain cells specific and EVs types (based in the origin or in the size of EVs) in the initiation, exacerbation, and propagation of the neurotoxic effects (inflammation, neurodegeneration, and accumulation of neurotoxic proteins) induced by air pollution in the CNS. Additionally, we discuss the identification and isolation of neural-derived EVs from human plasma, the most common markers for neural-derived EVs, and their potential for use as diagnostic or therapeutic molecules for air pollution-related cognitive impairment and neurodegeneration.

Evaluation of the antifungal and plasma membrane H+-ATPase inhibitory action of ebselen and two ebselen analogs in S. cerevisiae cultures.

The plasma membrane H(+)-ATPase pump (Pma1p) has been proposed as a viable target for antifungal drugs since this high capacity proton pump plays a critical role in the intracellular regulation of pH and in nutrient uptake of yeast and other fungi. In recent years, this and other laboratories have verified that the antifungal activity of 2-phenylbenzisoselenazol-3(2H)-one, an organoselenium compound commonly referred to as ebselen (1), stems, at least in part, from its inhibitory action on the fungal Pma1p. In the present study, the antifungal efficacy of 2-(3-pyridinyl)-benzisoselenazol-3(2H)-one (2) and 2-phenylbenzisoselenazol-3(2H)-one 1-oxide (3), two ebselen analogs, was evaluated using a strain of S. cerevisiae and compared against that of 1. In addition, the study also examined the inhibitory potential of these three compounds toward the Pma1p of S. cerevisiae. Based on mean IC(50) values, the antifungal potency was found to decrease in the order 3 > 1 > 2. However, in terms of inhibitory action on Pma1p, the potency decreased in the order 1 > 3 > 2. The magnitude of these activities appears to be correlated with the corresponding log P values, with compound 2 being the most hydrophilic and the least active of the three.

Design, synthesis and determination of antifungal activity of 5(6)-substituted benzotriazoles.

In an effort to find inhibitors that are effective against both Candida and Aspergillus spp., a series of 5(6)-(un)substituted benzotriazole analogs, represented by compounds 3a-3h and 3b'-3f', were prepared using a crystalline oxirane intermediate 1 previously synthesized in our laboratory. All the compounds were evaluated for inhibitory activity against various species of Candida and Aspergillus. Compounds 3b' (5,6-dimethylbenzotriazol-2-yl derivative), 3d (5-chlorobenzotriazol-1-yl derivative) and 3e' (6-methylbenzotriazol-1-yl derivative) exhibited potent antifungal activity, with the MICs for Candida spp. and Aspergillus niger, ranging from 1.6 microg/mL to 25 microg/mL and 12.5 microg/mL to 25 microg/mL, respectively. The present work describes the design, synthesis, regioisomer characterization (through COSY and NOESY 2D-NMR spectroscopy and single molecule X-ray crystallography), antifungal evaluation, molecular docking, and structure-activity relationships of the various 5(6)-(un)substituted benzotriazole analogs.