Proposal of a new, fast, cheap, and easy method using DLLME for extraction and preconcentration of diazepam and its transformation products generated by a solar photo-Fenton process.

This work evaluated the formation of transformation products (TPs) during the degradation of diazepam (DZP) by a solar photo-Fenton process. Six TPs were identified, three of them for the first time. After elucidation of the TPs, a new, cheap, fast, and easy method was employed to extract and preconcentrate DZP and its TPs, using dispersive liquid-liquid microextraction (DLLME). The method was optimized using factorial and Doehlert designs, with the best results obtained using acetonitrile as disperser solvent and chloroform as extraction solvent, with volumes of 1000 and 650 µL, respectively. When DZP degradation was performed in ultrapure water, the extraction/preconcentration of DZP and its TPs by DLLME was very similar to the results obtained using a traditional SPE method. However, when hospital wastewater was used as the matrix, more limited extraction efficiency was obtained using DLLME, compared to SPE. Meanwhile, all the TPs extracted by SPE were also extracted by the DLLME technique. Furthermore, DLLME was much less expensive than SPE, besides being faster, easier, and requiring only small amounts of organic solvents. This work reports a new and very important tool for the extraction and preconcentration of TPs formed during degradation using techniques such as advanced oxidation processes (AOPs), since without this step it would not be possible to identify all the TPs formed in some complex wastewater matrices.

Design, synthesis, cholinesterase inhibition and molecular modelling study of novel tacrine hybrids with carbohydrate derivatives.

A series of hybrids containing tacrine linked to carbohydrate-based moieties, such as d-xylose, d-ribose, and d-galactose derivatives, were synthesized by the nucleophilic substitution between 9-aminoalkylamino-1,2,3,4-tetrahydroacridines and the corresponding sugar-based tosylates. All compounds were found to be potent inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in the nanomolar IC50 scale. Most of the d-xylose derivatives (6a-e) were selective for AChE and the compound 6e (IC50 = 2.2 nM for AChE and 4.93 nM for BuChE) was the most active compound for both enzymes. The d-galactose derivative 8a was the most selective for AChE exhibiting an IC50 ratio of 7.6 for AChE over BuChE. Only two compounds showed a preference for BuChE, namely 7a (d-ribose derivative) and 6b (d-xylose derivative). Molecular docking studies indicated that the inhibitors are capable of interacting with the entire binding cavity and the main contribution of the linker is to enable the most favorable positioning of the two moieties with CAS, PAS, and hydrophobic pocket to provide optimal interactions with the binding cavity. This finding is reinforced by the fact that there is no linear correlation between the linker size and the observed binding affinities. The majority of the new hybrids synthesized in this work do not violate the Lipinski's rule-of-five according to FAF-Drugs4, and do not demonstrated predicted hepatotoxicity according ProTox-II.

Selenofuranoside Ameliorates Memory Loss in Alzheimer-Like Sporadic Dementia: AChE Activity, Oxidative Stress, and Inflammation Involvement.

Alzheimer's disease (AD) is becoming more common due to the increase in life expectancy. This study evaluated the effect of selenofuranoside (Se) in an Alzheimer-like sporadic dementia animal model. Male mice were divided into 4 groups: control, Aß, Se, and Aß + Se. Single administration of Aß peptide (fragments 25-35; 3 nmol/3 µL) or distilled water was administered via intracerebroventricular (i.c.v.) injection. Selenofuranoside (5 mg/kg) or vehicle (canola oil) was administered orally 30 min before Aß and for 7 subsequent days. Memory was tested through the Morris water maze (MWM) and step-down passive-avoidance (SDPA) tests. Antioxidant defenses along with reactive species (RS) were assessed. Inflammatory cytokines levels and AChE activity were measured. SOD activity was inhibited in the Aß group whereas RS were increased. AChE activity, GSH, and IL-6 levels were increased in the Aß group. These changes were reflected in impaired cognition and memory loss, observed in both behavioral tests. Se compound was able to protect against memory loss in mice in both behavioral tests. SOD and AChE activities as well as RS and IL-6 levels were also protected by Se administration. Therefore, Se is promising for further studies.