Benzodioxol Group Driving Supramolecular Arrangement of Two Tri-Methoxy Chalcones onto Β-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 P2 1 /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 .

A new isostructural halogenated chalcone with optical properties

“…8). For both solid-state systems, the intermolecular interactions and topography follow the same pattern [2,21,62]. Table 2 shows the non-classical interactions of CLC and BRC crystals, as well as the distances of the bonds.…”

“…Chalcones are a group of organic compounds derived from natural products, which can be obtained synthetically. They consist of two aromatic rings linked by an α, β unsaturated carbonyl system [1][2][3]. Chalcones have many biological activities, such as anticancer, anti-inflammatory, antioxidant, antifungal, and antidiabetic activities [4][5][6][7][8][9].…”

Arylsulfonamide chalcones as alternatives for fuel additives: antioxidant activity and machine learning protocol studies

“…Small differences, such as the position of a substituent or different substituents in the same position, can corroborate different conformations of the molecule, different interactions, and supramolecular arrangements. 104–108…”

“…42,[47][48][49][50][51] The structure-activity relationship of a molecule is often favored by substitution with bioactive chemical groups, which can potentiate the molecular activity. [52][53][54] The sulfonamide group is an example of a chemical group that is reported in the literature to have several biological properties, including antimicrobial [55][56][57] and antioxidant activities. [58][59][60][61] Therefore, the replacement of this group in chalcone molecules can be structurally innovative toward antioxidant activities.…”

A Comprehensive Topological Analysis on a New Bromine-Chalcone with Potential Nonlinear Optical Properties

“…The topological analysis can be realized by QTAIM methodology. According to the mechanical-quantum concepts for this methodology, the observable properties are present in its molecular electron density [ρ­( r )] that is used for the execution of numerical integrations with the gradient vector [∇ρ­( r )] as the basic condition for determining molecular topology. , The binding energies of the C–Br···π, C–H···Br, and C–H···O interactions were calculated at the B3LYP/6-311++G­(d,p) theory level using the DFT coupled in the Gaussian09 package, and from the generated wave function was performed the topological analysis of the interactions − by Multiwfn software …”