In silico Studies of Saponins from Hoya Verticillata var. Verticillate with Important Apoptosis Potency

Steroidal saponins are natural compounds known to have anticancer activity by inducing apoptosis through inhibition of Bcl-2. This study was carried out on the potency, mechanism, and binding affinity of steroidal saponins present from Hoya verticillata var. verticillata as Bcl-2 inhibitor of colorectal cancer in silico using molecular docking and molecular dynamics simulation. All steroidal saponins exhibited hydrogen bonds in molecular docking, Van der Waals, and hydrophobic interactions. The binding potentials of steroidal saponins collected in previous studies and a reference compound, navitoclax, as target protein 6GL8 of BCL-2 inhibitor of colorectal cancer, were examined using molecular docking. The results showed the binding stabilities as -8.28, -8.87, -9.29, -11.09, - 11.16, and -8.34 kcal/mol, respectively. Given the limited in-silico studies on pregnane saponins, we considered the extensive interest in these compounds. So, molecular dynamics studies were carried out to better comprehend the dynamics of ligands within the binding pocket of the target protein. Molecular dynamics simulation revealed that the binding of parasiticoside B to the 6GL8 receptor was stable and strong, based on their RMSD, RMSF, and the number of hydrogen bonds throughout the simulation. From the molecular interaction analysis derived from molecular dynamic trajectories of each ligand-bound complex, these interacting amino acids might be determined to play a crucial role in binding with the ligands of the 6GL8 active site. Parasiticoside B could be a good candidate for new inhibitors of anti-apoptotic BCL-2 proteins in colorectal cancer.