Halogen Bonding on Water─A Drop in the Ocean?

Halogen bonding is a valuable interaction in drug design, offering an unconventional way to influence affinity and selectivity by leveraging the halogen atoms' ability to form directional bonds. The present study evaluates halogen-water interactions within protein binding sites, demonstrating that targeting a water molecule via halogen bonding can in specific cases contribute beneficially to ligand binding. In solving and examining the crystal structure of 2-cyclopentyl-7-iodo-1-indole-3-carbonitrile bound to DYRK1a kinase, we identified a notable iodine-water interaction, where water accepts a halogen bond with good geometric and energetic features.

Substrate-Based Ligand Design for Phenazine Biosynthesis Enzyme PhzF.

The phenazine pyocyanin is an important virulence factor of the pathogen Pseudomonas aeruginosa, which is on the WHO list of antibiotic resistant "priority pathogens". In this study the isomerase PhzF, a key bacterial enzyme of the pyocyanin biosynthetic pathway, was investigated as a pathoblocker target. The aim of the pathoblocker strategy is to reduce the virulence of the pathogen without killing it, thus preventing the rapid development of resistance.

Prolonged release from lipid nanoemulsions by modification of drug lipophilicity.

In addition to the solubilization of poorly water-soluble, highly lipophilic drugs, lipid nanoemulsions bear potential for drug targeting approaches. This requires that the drug remains within the emulsion droplets until they reach the site of action. Since drug release is rather controlled by the lipophilicity of the drug than by the formulation, this study systematically investigated the influence of drug lipophilicity on the course of drug transfer in (physiological) acceptor media.

The indole motif is essential for the antitrypanosomal activity of N5-substituted paullones.

Severe infections with potentially fatal outcomes are caused by parasites from the genera Trypanosoma and Leishmania (class Kinetoplastea). The diseases affect people of remote areas in the tropics and subtropics with limited access to adequate health care. Besides insufficient diagnostics, treatment options are limited, with tenuous developments in recent years.