In silico screening of anti-cancer potential of acetogenins by induced apoptosis and molecular docking with intrinsic pathway markers

Background: Programmable cell death, or apoptosis, is one of the most appealing targets for anti-cancer treatment. Normally, in cancer, the highly complex and sophisticated mechanism of apoptosis is dysregulated by various means. Inducing apoptosis through plant-derived compounds that possess anti-cancer characteristics is currently emerging as a novel anti-cancer therapy. Objective: In this study, in silico screening of acetogenins was performed to identify their potency in inducing apoptosis via intrinsic pathway markers, namely p53, caspase-9, and cdk2, in cancerous cells. Methods: Autodock vina was employed to perform in silico molecular docking analysis. The resultant structures were examined using Biovia Discovery Studio and PyMol software. Docking validation was executed using DINC. Result: Molecular docking results revealed that acetogenins such as annohexocin, annomuricin A, annomutacin A, and murihexocin exhibited better binding interactions, using a cut-off greater than –5 kcal/mol, with the target proteins, namely CASP9, CDK2, and TP53 (both wild-type and mutant), with paclitaxel and gefitinib as standard drugs. The docked complex of protein targets with the standard drugs gefitinib and paclitaxel showed fewer fluctuations in RMSD values, with the best binding energy near zero, confirming the performance of accurate molecular docking. Conclusion: Plants from the family Annonaceae have been reported to have a wide spectrum of therapeutic benefits against various human cancers, which entails a promising anti-cancer molecule, acetogenin. Acetogenin, which is a potent inducer of apoptosis when used as a ligand in molecular docking, exhibited promising binding affinity towards proteins associated with the intrinsic pathway of apoptosis, suggesting their potential effectiveness against breast cancer.