Benzodioxol group driving supramolecular arrangement of two tri-methoxy chalcones onto Beta-Secretase 1 enzyme active site

Abstract

Chalcones are compounds with wide interesting biological activities including Alzheimer's disease. A comparative study was performed between the chalcones (E)-1-(2-aminophenyl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one and 1-(6-amino-1,3-benzodioxol-5-yl)- 3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one regarding the influence of benzodioxol group on their molecular conformations. The first chalcone was neutralized with dilute hydrochloric acid, while solid of the second was filtered and recrystallized from ethanol, both on centrosymmetric space group P21/c. Their molecular packing were evaluated by Hirshfeld surfaces, and both frontier molecular orbitals and molecular electrostatic potential (MEP) map were carried out by density functional theory (DFT) calculations. The compounds are stabilized by C-H⋯O and C-H⋯π interactions, as observed on MEP map, while the HOMO-LUMO gap indicated the conformational stability. The pharmacophore mapping approach was carried out for the identification of potential target candidates and then, further molecular docking analysis targeting the beta-secretase 1 (BACE-1) protein as a tactic to develop potential AD inhibitors, was performed. The AutoDock Vina score in redocking result for 2OHQ is -7.4 and -7.6 kcal mol-1. Additionally, the docking results for compounds inside the active site of the 2OHQ structure showed that both compounds bound to the BACE-1 active site with AutoDock Vina score of -6.0 kcal mol-1