Probing the bioactive compounds of as novel inhibitors of TNF-α converting enzyme using HPLC/GCMS analysis, FTIR and molecular modelling.

Tumor Necrosis Factor Alpha Converting Enzyme (TACE) mediates inflammatory disorder and contributes to the pathophysiology of a variety of illnesses, such as chronic inflammation and cancer. This study identified metabolites in solvent extracts of as putative TACE inhibitors due to the plant's known anti-inflammatory properties. HPLC-MS/GCMS analysis was used to characterize tentative phytochemicals from . The identified metabolites (n = 123) were docked with TACE to reveal the lead compounds. Binding free energy, ADMET prediction, molecular dynamics simulation at 100 ns, and DFT calculation were further conducted. The results revealed that contains sterol, phenols, alkaloids, terpenes and flavonoids. The FTIR shows that the extracts had peaks that correspond to the presence of different functional groups. The quantum polarized ligand docking (QPLD) analysis identified compound (n = 3) with binding affinity higher than standard compound IK-682. The hits also had modest ADMET profiles, interacted with essential residues within TACE binding pockets, and formed stable complexes with the protein. The 100 ns MD simulation shows that the compounds formed fairly stable interactions and complex with the protein as evidenced through RMSF, RMSD and MM-GBA results. The HOMO/LUMO, global descriptive molecular electrostatic potential Fukui function aid in the identification of the compounds' atomic sites prone to electrophilic/neutrophilic attacks, and non-covalent interactions. This study suggests that bioactive compounds are capable of mitigating inflammation by inhibiting TACE.Communicated by Ramaswamy H. Sarma.