Theoretical investigations, Molecular Docking, ADMET analysis, Molecular Dynamic Simulation, and Drug-Likeness Scoring of (E)-1-[2-(3,4-Dimethylphenyl) Diazen-2-Ium-1-Yl] Naphthalen-2-Olate as a Corticosteroid Side-Chain-Isomerase Inhibitor

Year 2025, Volume: 9 Issue: 3, 57 - 78

Youcef Megrouss , Souheyla Chetioui , Chafika Farah Kaouche , Yahıaouı Salem , Khaled Drim , Zohra Douaa Benyahlou , Mansour Azayez , Sid Ahmed Kaas , Mokhtaria Drıssı , Abdelkader Chouaih

Abstract

In this article, the optimized structure and their associated properties of the (E)-1-[2-(3,4-Dimethylphenyl)diazen-2-ium-1-yl]naphthalen-2-olate compound (EDNO) were obtained and evaluated using The density functional theory DFT at the (B3LYP/6-311G++(d,p)) level in the gas phase, To quantify the intermolecular interactions, Hirshfeld surface(HS) analysis was used, HS and 2D fingerprints indicate H⋅⋅⋅H (52%) and C− H⋅⋅⋅C (26.7%) as the most relevant intermolecular interactions in the crystal packing of EDNO. the reduced density gradient (RDG) method was used to reveal and distinguish between attractive interactions such hydrogen bonds, repulsive interactions and van der Waals interactions. Further, molecular docking, binding free energy calculations, and ADMET prole of the title compound was carried out to determine the binding affinity and toxicity. A 100 ns molecular dynamics (MD) simulation was performed to evaluate the binding stability of the compound EDNO/2WV2 complex using Desmond. Binding free energy of the complex was computed for 100 trajectory frames using the MM-GBSA approach

Keywords

Azo Compounds, Hirshfeld surface analysis, DFT calculations, ADMET; Molecular docking; MD simulation.

Thanks

I would like to thank the management of the Turkish computational and theoretical chemistry journal for its contribution to the dissemination of scientific research worldwide.

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