Evaluation of Novel Hydrazone-Imide Hybrid Compound as HNE Inhibitor In Silico: Synthesis, XRD and DFT Analysis

Abstract

Investigation into the interactions between drugs and biomolecules can offer a precise understanding of their biological behaviours in vitro and in vivo, providing crucial insights for designing new drugs. Herein, we report the design, synthesis, and characterization of a bicyclic hydrazone derivative, along with its potential as an inhibitor of human neutrophil elastase (HNE), a critical enzyme in the treatment of acute and chronic lung injuries. We present an improved protocol for the synthesis of the compound using N-amino-bicyclo[2.2.1]hept-5-ene-2,endo-3-endo-dicarboximide and 4-(trifluoromethyl)benzaldehyde through a facile, one-pot, catalyst-free synthesis in dry ethanol at reflux temperature. Within 12 hours, bicyclic-hydrazone derivative was obtained with yields of up to 75 % and was characterized using various spectroscopic techniques and computational analyses based on the DFT approach. In silico ADME/T profile of the compound was evaluated and molecular docking simulation was utilized to predict its potential as a HNE inhibitor. The binding energy values of the THI ligand to the chosen PDB ID: 5ABW, 3Q77, and 2RG3 target proteins were determined as -8.41, -7.20, and -7.27 kcal/mol, respectively. In silico analysis findings indicate that the THI compound has promising drug-likeness properties and has the potential to be evaluated in the development of new HNE inhibitors.