Quantum-chemical and docking studies of 8-hydroxy-quinolines as inhibitors of the botulinum neurotoxin a light chain (BoNT/A LC)

Juan S. Gómez

Abstract

We have analyzed the relationships between the electronic structure of a group of 8-hydroxy-quinolines and the decrease in BoNT/A LC enzymatic activity toward the SNAPtide substrate. The electronic structure of the molecules was obtained after full geometry optimization with Density Functional Theory at the 6-31G(d,p) level. The statistically significant relationship obtained explains very well the variation of the inhibitory activity in this group. The corresponding inhibitory pharmacophore was built. Also we analyzed the docking of the R and S isomers with a model of the Clostridium Botulinum serotype A light chain. The analysis of the docking results with a simple model of the space surrounding the binding site allowed us to select two sets of molecules that could have high affinity.