Cytotoxic Activity and Molecular Docking of Indole Alkaloid Voacangine, Bis-indole Alkaloids Vobtusine, and Vobtusine Lactone from the Indonesian Plant: Voacanga foetida (Blume) Rolfe

The purpose of this study was to evaluate the in vitro cytotoxic activity of two isolated compounds from Voacanga foetida (Blume) Rolfe against the A549 cell line. The in silico study was carried out to predict the cytotoxic mechanism of two isolated compounds (vocangine and vobtusine lactone) and previously reported compound (vobtusine) against pro-survival receptors (Bcl-2, Bcl-xL, Mcl-1), pro-activation receptor (Bax), and apoptotic execution receptor (caspase-3). This research is an experimental quantitative using column chromatography and HPLC methods in the isolation process, MTT assay in determining the cytotoxic activity, and molecular docking in determining the prediction of ligand-receptor interactions. The fractions (VFB-DA, VFB-DB, VFB-BuOH, VFB-DB4) and voacangine exhibited very strong cytotoxic activity, while vobtusine lactone showed moderate cytotoxic activity. The docking scores for voacangine, vobtusine, and vobtusine lactone against Bcl-2 were -9.93; -10.07; -9.03 kcal/mol, against Bcl-xL were -9.77; 11.69; -9.76 kcal/mol, against Mcl-1 were -10.70; -10.77; -9.53 kcal/mol, and for Bax were -8.99; -6.87; -6.99 kcal/mol, as well as against caspase-3 were12.05; -12.21; -12.02 kcal/mol. The cytotoxic activity of voacangine, vobtusine, and vobtusine lactone was thought to cause cell death by suppressing Bcl-xL and Mcl-1 activities and also increasing Bax and caspase3 activities.