Chemical Biology & Drug Design

This current study explores a new class of GCP II inhibitors, glutamyl sulfamides, which possess a neutral tetrahedral zinc-binding motif. A small library containing 6 sulfamides was prepared and evaluated for inhibitory potency against purified GCPII. While most inhibitors have potencies in the micromolar range, one showed promising sub-micromolar potency, with the optimal inhibitor in this series being aspartyl-glutamyl sulfamide

This study was focused on the evaluation of efficiency of synthesized resistance-nodulation-division (RND) family efflux pump inhibitors. Efficiency of the synthesized compounds was investigated on Salmonella enterica ser. Typhimurium cells using electrochemical and spectrofluorimetric methods. The results obtained showed that the registered efficiency of inhibitors depends on the permeability of cell outer membrane and the method of assay used.

Virtual screenings were performed on ABL1 kinase to study inhibitors for wild type T315 mutant form. In addition, chemoinformatic methods were also applied on kinase inhibitors. We show that VS and ligand-based studies are complementary in understanding the features that should be considered during in silico studies.

The first example of an inhibitor of the kinase TAK1 that binds in the DFG-out conformation is disclosed. These preliminary studies used kinase-targeted screening and structure-based drug design to create a molecule with dual pharmacological inhibition of p38 and TAK1 that demonstrated significant activity in a cell-based, anti-inflammatory assay.

Preptin analogues with non-protein amino acids have been chemically synthesized, characterized and analysed for their ability ability to augment insulin secretion from βTC6-F7 β-cells.