Anti-breast cancer potential activity of Phaleria macrocarpa (Scheff.) Boerl. leaf extract through in silico studies

Context: The development of apoptotic agent from natural plant products may have a beneficial effect as a promising candidate for cancer therapy. The study about the efficacy of Phaleria macrocarpa leaves on breast cancer is still limited. Aims: To elucidate the molecular mechanisms underlying the anti-breast cancer activity of P. macrocarpa leaves extract by in silico analysis. Methods: The compounds of the ethanol extract of P. macrocarpa were identified by Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS) analysis. Fourteen bioactive compounds of P. macrocarpa leaf were analyzed to determine the biological activity using Prediction of Activity Spectra for Substances (PASS) server. The network analysis was analyzed using STRING (https://string-db.org/). Twelve selected compounds were docked with several protein targets, including caspase 3, Bax and Bcl-2. Molecular docking was done by Pyrx 0.8 software and visualized by Discovery Studio software. The pharmacological properties of investigated bioactive compounds were analyzed using the SwissADME web server. Results: The twelve from fourteen bioactive compounds of P. macrocarpa leaf have anticancer properties and might be expected to involve in p53 and PI3K/Akt signaling pathways related to cancer. The molecular docking result showed that sesamin from the lignans group has the best binding affinity to caspase-3 and Bax. Meanwhile, corymboside from the flavonoid group has the best binding affinity to Bcl-2. Conclusions: The bioactive compounds of P. macrocarpa leaves extract might potentially modulate apoptosis and cell growth. Further research should be performed to validate the activity of P. macrocarpa bioactive compounds for target cancer development.