Employing Molecular Docking Calculations for the Design of Alkyl (2-Alcoxy-2-Hydroxypropanoyl)-L-Tryptophanate Derivatives as Potential Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1)

Abstract

In this paper, we presented the design by computational tools of novel alkyl (2-alcoxy-2-hydroxypropanoyl)-L-tryptophanate derivatives, which can be potential inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The molecular structure optimization of a group of 36 compounds was performed employing DFT-B3LYP calculations at the level 6-311G(d,p). Then, molecular docking calculations were performed using Autodock tools software, employing the Lamarckian genetic algorithm (LGA). Four parameters (binding, intermolecular and Van Der Waals hydrogen bonding desolvation energies, and HOMO-LUMO gap) were used to evaluate the potential as 11β-HSD1 inhibitors, which nominate L-tryptophan derivatives as the most promissory molecules. Finally, these molecules were obtained starting from the amino acid and pyruvic acid in a convergent methodology with moderate to low yields.