Anthrax Lethal Factor Protease Inhibitors: synthesis, SAR and Structure-based 3D QSAR studies

We have recently identified a series of compounds that efficiently inhibit anthrax lethal factor (LF) metallo-protease. Here we present further structure-activity relationship and CoMFA (comparative mol. field anal.) studies on newly derived inhibitors. The obtained 3D QSAR model was subsequently compared with the X-ray structure of the complex between LF and a representative compounds. Our studies form the basis for the rational design of addinional compounds with improved activity and selectivity.