In silico exploration of anti-lung cancer activity of selected steroidal saponins via anti-apoptotic pathway

Vollständiger Abstract

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Lung cancer is the leading cause of cancer death in the world. Inhibition of apoptosis involves blocking the cell’s natural process of self-destruction. This can occur through various mechanisms including the action of proteins like Bcl-2 family members and apoptosis inhibitors and growth factor upregulation. This study performed molecular docking, molecular dynamics simulation and ADMET prediction on eleven steroidal saponins isolated from Paris rugosa as potential apoptosis inhibitors for lung cancer treatment. The molecular docking results showed that ophiopogonin C’ and 17-hydroxygracillin are more stable and are better localized within the 6GL8 protein pocket. The molecular dynamics simulation results reveal a persistent inhibition mode and consistent binding interactions in all simulations. These findings indicated that the binding of all selected compounds to 6GL8 protein was stable during 100 ns molecular dynamics simulation. The in silico ADMET prediction was further carried out to evaluate the oral bioavailability of selected compounds. As a result, ophiopogonin C’ satisfies all the pharmacokinetic criteria, which are non-toxic, have superior distribution capacity and have high absorption. This steroidal saponin is an inhibitor of the anti-apoptotic protein Bcl-2 (6GL8), serving as a promising candidate for the development of future drugs to treat human lung cancer.