Molecular modelling studies

The Schrödinger Suite was adopted for computing all theoretical investigations (Software: Schrödinger, LLC, New York, NY. 2017). The 3D structure of AC-18, AC-20 and AC-22 were built using the Maestro GUI (Software: Maestro Schrödinger, LLC, New York, NY. 2017) and further submitted to LigPrep version 3.9 tool (Software: LigPrep Schrödinger, LLC, New York, NY. 2017) to take into account the most stable protomeric forms at pH 7.4. The Protein Data Bank (https://www.rcsb.org/) crystallographic entry structure 2PRG (Nolte et al., 1998) was prepared by using the Protein Preparation Wizard tool (Schrödinger, LLC, New York, NY, 2017). The molecular recognition evaluation was carried out by means of Glide software ^[g] in combination with Schrödinger Induced Fit docking (IFD) (Glide Schrödinger, LLC, New York, NY, 2017) protocol. The binding site of the target model was defined by means of a regular grid box of about 64,000 Å centered on the co-crystallized ligand. Docking simulations were computed using Glide ligand flexible algorithm version 6.7 at standard precision (SP).