Development of Urease Inhibitors by Fragment-Based Dynamic Combinatorial Chemistry

Abstract

In this study, fragment-based dynamic combinatorial chemistry (DCC) was explored for the development of novel urease inhibitors. Based on a rationally designed fragment, two iteratively evolved dynamic combinatorial libraries (DCLs) were generated and screened in the presence of urease template. The best ligand identified revealed not only strong urease inhibition but also low cytotoxicity. Additionally, a possible inhibitory mechanism was elucidated in the binding kinetics study and docking simulation.

Keywords: Dynamic combinatorial chemistry; Fragment-based drug design; Kinetic analysis; Molecular docking; Urease inhibition.