A new chalcone derivative: Synthesis, crystal structure, Hirshfeld surface, quantum chemical investigations, Druggability and human Cathepsin D inhibitory activity

Abstract

This paper presents the synthesis of a novel chalcone derivative, and its molecular structure has been determined by NMR and single-crystal X-ray diffraction analysis. The molecules are connected via OH⋅⋅⋅O, CH⋅⋅⋅O, and CH⋅⋅⋅S hydrogen bonds along with CH⋅⋅⋅π and π⋅⋅⋅π interactions. Hirshfeld surface studies have been conducted to comprehensively quantify the patterns of intermolecular interactions. DFT calculations provided insights into the nature of the molecule, including frontier molecular orbital, ADCH charge, Molecular Electrostatic Potential and Natural Bond Orbitals analysis using the optimized structure by B3LYP/6–311 G (d, p) level. The calculated HOMO-LUMO gap (3.23 eV) indicates decent softness and reactivity of the target molecule. The molecular docking studies reveal that the target compound exhibits a high binding affinity with Human Cathepsin D (CatD), with a docking score of -7.58 kcal/mol. The assessment of drug-likeness properties and ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiles further support its potential as a potent CatD inhibitor candidate for medication development.