5-HT6 receptor antagonists. Design, synthesis, and structure-activity relationship of substituted 2-(1-methyl-4-piperazinyl)pyridines.

In this study, we present the discovery and pharmacological characterization of a new series of 6-piperazinyl-7-azaindoles. These compounds demonstrate potent antagonism and selectivity against the 5-HT6 receptor. Our research primarily focuses on optimizing the lead structure and investigating the structure-activity relationship (SAR) of these compounds. Our main objective is to improve their activity and selectivity against off-target receptors. Overall, our findings contribute to the advancement of novel compounds targeting the 5-HT6 receptor. Compound 29 exhibits significant promise in terms of pharmacological, physicochemical, and ADME (Absorption, Distribution, Metabolism, and Excretion) properties. Consequently, it merits thorough exploration as a potential drug candidate due to its favorable activity profile and successful outcomes in a range of in vivo experiments.

The effect of an acid catalyst on the hydrothermal carbonization of sewage sludge.

This research is focused on the addition of a catalyst, sulphuric acid (VI), to sewage sludge, and its effect on solid and liquid products resulting from the hydrothermal carbonization process. Consequently, for hydrochars, proximate and ultimate analyses, higher heating value and specific surface area were determined. Additionally, Fourier-transform infrared spectrophotometric and thermogravimetric analyses were conducted. The heavy metal contents in the ash composition of hydrochars were identified by X-ray fluorescence spectrometry. It was confirmed that the catalyst addition changed the structure as well as the physical and chemical properties of hydrochars and their ashes. Regarding post-processing water, both pH value and conductivity were determined and the element composition, including heavy metals, was conducted by the inductively coupled plasma optical emission and mass spectrometry analyses. It was found that the addition of the catalyst caused a decrease in heavy metal contents and an increase of phosphorus compound in filtrates.

Life cycle assessment of the hydrothermal carbonization process applied to the wet fraction mechanically separated from municipal mixed waste.

The under-sieve fraction (USF), obtained as one of the output streams from the mechanical pretreatment of mixed municipal solid waste, is usually aerobically biologically stabilized before being landfilled. For its characteristics (i.e., moisture and organic content), the USF can be alternatively processed by hydrothermal carbonization (HTC), producing hydrochar to be used for energy production. Based on previous results obtained from laboratory HTC tests of the USF, this work is aimed at evaluating the sustainability of the proposed process from an environmental point of view by applying the Life Cycle Assessment. Various combinations of process parameters (temperature, time, and dry solid-to-water ratios) and two different utilization pathways for hydrochar (the whole amount produced in external lignite power plants or part of it used internally) are compared. The results indicate that environmental performances are mainly connected with process energy consumption: in general, the cases operating at the lowest dilution ratio and the highest temperature provide improved environmental indicators. Co-combusting all the produced hydrochar in external power plants provides better environmental performances than feeding a portion of it to the HTC itself: the avoided effects by displacing lignite are higher than the additional burdens from natural gas use. Then, alternative process water treatments are compared, showing that the burdens added by the process water treatments do not offset the benefits generated by the main HTC process for the major part of the considered environmental indicators. Finally, the proposed process indicates better environmental performances when compared to the conventional method of treating the USF, based on aerobic biostabilization and landfilling.

The treatment of post-processing liquid from the hydrothermal carbonization of sewage sludge.

The liquid phase, being a major product of the hydrothermal carbonization of sewage sludge, is highly problematic due to numerous toxic compounds that make it impossible to dispose of without adequate purification. Therefore, this study is focused on the two groups of selected advanced methods of post-processing water derived from the hydrothermal carbonization process of sewage sludge. The first group included membrane processes, namely ultrafiltration, nanofiltration and double nanofiltration. The second included coagulation, ultrasonication and chlorination. Chemical and physical indicators were determined to confirm the validity of these treatment methods. The highest reduction values were found for double nanofiltration, which showed a spectacular decrease in the Chemical Oxygen Demand by 84.9 %, specific conductivity by 71.3 %, nitrate nitrogen by 92.4 %, phosphate phosphorus by 97.1 %, total organic carbon by 83.3 %, total carbon by 83.6 %, and inorganic carbon by 88.5 %, as compared to the liquid phase after hydrothermal carbonization. In the second group, for the largest number of parameters, the greatest reduction was achieved when 10 cm3/L of iron coagulant was added to the permeate from ultrafiltration. Additionally, COD decreased by 41 %, P-PO43- content by 78 %, phenol content by 34 %, TOC content by 97 %, TC content by 95 % and IC content by 40 %.

5-Keto-3-cyano-2,4-diaminothiophenes as selective maternal embryonic leucine zipper kinase inhibitors.

Maternal embryonic leucine zipper kinase (MELK) is involved in several key cellular processes and displays increased levels of expression in numerous cancer classes (colon, breast, brain, ovary, prostate and lung). Although no selective MELK inhibitors have yet been approved, increasing evidence suggest that inhibition of MELK would constitute a promising approach for cancer therapy. A weak high-throughput screening hit (17, IC50 ≈ 5 µM) with lead-like properties was optimized for MELK inhibition. The early identification of a plausible binding mode by molecular modeling offered guidance in the choice of modifications towards compound 52 which displayed a 98 nM IC50. A good selectivity profile was achieved for a representative member of the series (29) in a 486 protein kinase panel. Future elaboration of 52 has the potential to deliver compounds for further development with chemotherapeutic aims.