Rational design, synthesis and pharmacological characterization of novel aminopeptidase A inhibitors.

Aminopeptidase A (APA) is a membrane-bound zinc metallopeptidase involved in the production of angiotensin III, one effector peptide of the brain renin-angiotensin system, making brain APA a relevant pharmacological target for the development of novel therapeutic treatments against hypertension and heart failure. The structure-based design of new APA inhibitors is described, based on previously developed thiol-containing inhibitors and APA crystal structure. Chemical synthesis, in vitro assessment against APA activity, pharmacological and pharmacokinetic profiling were performed, ultimately leading to a potent and selective APA inhibitor.

Discovery of BI-9508, a Brain-Penetrant GPR88-Receptor-Agonist Tool Compound for Mouse Studies.

Decreased activity and expression of the G-protein coupled receptor GPR88 is linked to many behavior-linked neurological disorders. Published preclinical GPR88 allosteric agonists all have pharmacokinetic properties that preclude their progression to the clinic, including high lipophilicity and poor brain penetration. Here, we describe our attempts to improve GPR88 agonists' drug-like properties and our analysis of the trade-offs required to successfully target GPR88's allosteric pocket.

Contamination of water, soil, and plants by micropollutants from reclaimed wastewater and sludge from a wastewater treatment plant.

Several studies have shown that plants can absorb various micropollutants. The behavior of micropollutants from wastewater treatment plant resources was comprehensively investigated in raised beds in which either a mixture of vegetables or maize was grown. The beds were either irrigated with treated wastewater or enriched with sewage sludge or composted sewage sludge.

Dissipation of twelve organic micropollutants in three different soils: Effect of soil characteristics and microbial composition.

The dissipation kinetics and half-lives of selected organic micropollutants, including pharmaceuticals and others, were systematically investigated and compared among different soil types. While some pollutants (e.g.

Selective accumulation of pharmaceutical residues from 6 different soils by plants: a comparative study on onion, radish, and spinach.

The accumulation of six pharmaceuticals of different therapeutic uses has been thoroughly investigated and compared between onion, spinach, and radish plants grown in six soil types. While neutral molecules (e.g.