Density Functional Theory and Spectroscopic Analysis of Stigmasterol from Garcinia wightii: Deciphering its Inhibitory Potential against Drug-Resistant Tuberculosis via Insilico Molecular Docking and Molecular Dynamics Simulations

This study investigates the molecular structure and electronic properties of stigmasterol, isolated from Garcinia wightii, using density functional theory (DFT) alongside experimental techniques including FT-IR, FT-Raman, UV–Vis, 1H and 13C NMR spectroscopy. Theoretical predictions are compared with experimental results, facilitated by vibrational energy distribution analysis for unambiguous vibrational wavenumber assignments. Natural bond orbital analyses reveal donor-acceptor bond energies and electron densities, while Fukui functions identify reactive sites susceptible to electrophilic and nucleophilic attacks. Electronic properties are further explored through various analyses, unveiling reactive surface sites. Non-covalent interactions are examined using reduced density gradient analysis. Assessment of absorption, distribution, metabolism, and excretion attributes aids in drug discovery efforts. Molecular docking studies against 20 target proteins for antitubercular screening show a stable glide score of -9.52 kcal/mol for the protein 4FDO (Mycobacterium tuberculosis DprE1 in complex with CT319). Molecular dynamics simulations over 100 ns indicate the stability of the ligand-protein complex, suggesting its potential as an antituberculosis agent. Stigmasterol's structural, vibrational, electronic, and topological properties are thoroughly investigated, revealing its ring skeleton with a flexible isooctyl side chain, adhering to C1 point group symmetry. Steric and stereo electronic interactions play crucial roles in conformation and binding to target proteins. Theoretical and experimental analyses align, confirming the compound's bioactive properties. This comprehensive investigation underscores stigmasterol's potential as a tuberculosis treatment option, providing valuable insights into its structural characteristics and therapeutic possibilities.