12 Years of honey surveys in northern Italy: How anthropic activities can influence honey quality.

Bees and hive products, such as honey, can act as indicators of environmental quality. Our research aimed to evaluate historical data of honey quality in Lombardy (Northern Italy) and consider the possible sources of air contamination that can influence it. We collected analytical data from the local Health Protection Agency on residues of 57 honey samples from 2011 to 2022, comparing a rural area and an industrial area. At the same time, we consulted estimated air emissions in the same areas through the INEMAR database used by the local Environmental Protection Agency. Data revealed antibiotic contamination in one case and, regarding heavy metals, lead contamination in several samples in the industrial area. Pb contamination could derive from multiple sources. The INEMAR database permitted us to hypothesize that combustion in industry and road transportation could have a role in honey contamination, being among the main sources of Pb emission in that area.

Recent advances in urea- and thiourea-containing compounds: focus on innovative approaches in medicinal chemistry and organic synthesis.

Urea and thiourea represent privileged structures in medicinal chemistry. Indeed, these moieties constitute a common framework of a variety of drugs and bioactive compounds endowed with a broad range of therapeutic and pharmacological properties. Herein, we provide an overview of the state-of-the-art of urea and thiourea-containing pharmaceuticals. We also review the diverse approaches pursued for (thio)urea bioisosteric replacements in medicinal chemistry applications. Finally, representative examples of recent advances in the synthesis of urea- and thiourea-based compounds by enabling chemical tools are discussed.

Exploiting Chemical Toolboxes for the Expedited Generation of Tetracyclic Quinolines as a Novel Class of PXR Agonists.

The discovery of lead compounds relies on the iterative generation of structure-activity relationship data resulting from the synthesis and biological evaluation of hit analogues. Using traditional approaches, a significant time delay may occur from compound design to results, leading to slow and expensive hit-to-lead explorations. Herein, we have exploited the use of chemical toolboxes to expedite lead discovery and optimization. In particular, the integration of flow synthesizers, automation, process analytical technologies, and computational chemistry has provided a prototype system enabling the multicomponent flow synthesis, in-line analysis, and characterization of chiral tetracyclic quinolines as a novel class of PXR agonists. Within 29 compounds, a novel template 19b (3aS,11R,11aS) was identified with an EC50 of 1.2 µM (efficacy 119%) at the PXR receptor.