Exploring the phytoconstituents targeting TNF-α as potential lead compounds to treat inflammatory diseases: an in-silico approach

Abstract

To explore the anti-inflammatory phytoconstituents from various plant sources as tumour necrosis factor- α (TNF- α )-inhibitor, a mediator involved in the inflammatory disorder, by in silico molecular docking. Based on previous findings, we performed the in silico assessment of anti-inflammatory phytoconstituents from different medicinal plants to understand their binding patterns against TNF- α (PDB ID: 6OP0) using AutoDock Vina. Molecular docking was performed by setting a grid box (25 × 25 × 25) Å centered at [– 12.817 × (– 1.618) × 19.009] Å with 0.375 Å of grid spacing. Furthermore, Discovery Studio Client 2020 program was utilized to assess two- and three-dimensional (2D and 3D) hydrogen-bond interactions concerning an amino acid of target and ligand. Physicochemical properties were reported using the Lipinski’s rule and SwissADME database to support the in silico findings. Results From the selected medicinal plants, more than 200 phytocompounds were screened against TNF- α protein with binding scores in the range of – 12.3 to – 2.5 kcal/mol. Amongst them, emodin, aloe-emodin, pongamol, purpuritenin, semiglabrin, ellagic acid, imperatorin, α -tocopherol, and octanorcucurbitacin A showed good binding affinity as – 10.6, – 10.0, – 10.5, – 10.1, – 11.2, – 10.3, – 10.1, – 10.1, and – 10.0 kcal/mol, respectively. Also, the absorption, distribution, metabolism, excretion, and toxicology (ADMET) profiles were well within acceptable limits. Based on our preliminary findings, we conclude that the selected phytoconstituents have the potential to be good anti-inflammatory candidates by inhibiting the TNF- α target. These compounds can be further optimized and validated as new therapeutic components to develop more effective and safe anti-inflammatory drugs. (i) Inflammation is a global clinical issue that involves several bio-chemical mediators. (ii) Phytoactive compounds are known to exhibit remarkable anti-inflammatory activities in traditional as well as some modern medicines. (iii) This study covers an in silico tool based findings that throw light on plant based bioactive compounds with potential for anti-inflammatory activity by inhibiting TNF- α. (iv) Precisely, 203 phyto-compounds were screened against target protein TNF- α trimer to find “best fit” based on docking score, binding energies, ADME studies, toxicity prediction, drug likeness, and molecular interactions.