Investigation of Some Substituted-Piperidine-3-carboxamide Derivative Compounds As Active Ingredients in the Treatment of Crohn’s Disease by Molecular Docking Method

Abstract

In this study, was investigated the feasibility of using some substituted piperidine-3-carboxamide derivative compounds, which have never been synthesized before and have not been included in the literature, for the treatment of Crohn’s disease, a chronic, inflammatory bowel disease that can affect any part of the digestive system, by molecular docking method. For this purpose, fifty different piperidine-3-carboxamide derivative molecules were used in molecular docking studies with nine different proteins using the Auto Dock Vina program. Among the molecules, the highest docking score of –12.8 kcal/mol was obtained between the compound 1-(2-{2-(4-bromophenyl)-4-[(E)-2-phenylhydrazinylidene]-1,2-dihydro-1,3,5-triazin-6-yl}ethyl)piperidine-3-carboxamide and the protein with PDB code 1KMV. Boiled-egg graphs and bioavailability radars were drawn for the ten molecules with the highest docking scores among the fifty studied molecules. Quantum mechanical parameters include highest occupied molecular orbital energy (E_HOMO), lowest unoccupied molecular orbital energy (E_LUMO), chemical potential (μ), electron affinity (EA), global softness (S), global hardness (η), ionization potential (IP), dipole moments, and electrophilicity (ω) were also analyzed. Finally, bond angles, bond lengths, and molecular electrostatic potential (MEP) were calculated, and a mechanism for the synthesis of this ideal molecule to be used in the treatment of Crohn’s disease was proposed.