Ganoderic acid modulating TNF and its receptors: in silico and in vitro study

摘要: Cancer is a multifactorial disease with network of genes causing genetic alterations. The sophisticated techniques in molecular biology revealed different cancer pathway, but their mechanistic approach still shrouded. Tumor necrosis factor and TNF-related apoptosis-inducing ligand receptors (DR5) emerged as potential target drug for the therapy. Among natural products basidiomycete fungus, Ganoderma lucidum its constituents endowed plethora activities modulating signaling cancer. Ganoderic acid, triterpene lanosteroidal skeleton play an inextricable role cascades various mitogenic pathways. In present study, receptor-based docking was performed to study dynamic behavior docked complexes interactions between ganoderic acid isoforms tumor receptor (DR5). top scoring compounds were compared already documented inhibitor factor, DR5-curcumin, catechin, bupropion, pentoxyphyllin binding affinity other absorption, distribution, metabolism, excretion, toxicity properties. A interact more promising GScore (−9.858 (kcal/mol), Lipophilic EvdW (−1.7), H Bond (−0.9), Glide emodel (−40.5) involvement Tyr 151, Leu 120 Gln 149 residues during factor. During DR5, exhibits (−8.7), HBond (−2.9), (−30.0) hydrogen bonding inMet99, Arg101, Pro97, Glu98 residues. Natural inhibitors exhibit low-binding energy parameters, which have edge DR5. efficiently inhibits proliferation, viability, intracellular reactive oxygen species messenger RNA expression DR5 breast cell lines.