Cytotoxic Evaluation, Molecular Docking, Molecular Dynamics, and ADMET Prediction of Isolupalbigenin Isolated from (Hassk). Merr. (Fabaceae) Stem Bark: Unveiling Its Anticancer Efficacy.

Introduction: , a medical plant found in sub-Saharan Africa and the Western Ghats of India, shows promise as a potential source of bioactive compounds to treat cancer. In our ongoing research on folk medical plants, we report the isolation of flavonoid compound from the stem bark of along with its cytotoxic activity against breast cancer (MCF-7 and T47D), and cervical cancer (HeLa) cell lines.

Purpose: This study aimed to isolate secondary metabolite from the stem bark of and evaluate its cytotoxic activity to support the use of folk medicinal plants as alternative therapy against cancer.

Methods: Isolupalbigenin was isolated from the stem bark of by column chromatography. Cytotoxic activity against breast cancer (MCF-7 and T47D) and cervical cancer (HeLa) cell lines was evaluated using the MTT assay, whereas the in silico study was evaluated using molecular docking and molecular dynamics against estrogen receptor alpha (ERα).

Results: The cytotoxic assay showed that isolupalbigenin inhibited the growth of MCF-7 cell with an IC of 31.62 µg∙mL, while showing no toxicity against normal human cells (Vero cell line). The molecular docking results suggested that isolupalbigenin can bind to ERα with a lower binding affinity than estradiol, whereas the stability of the isolupalbigenin-ERα complex was confirmed by molecular dynamic simulation with a median Root Mean Square Deviation (RMSD) of 2.80 Å. Toxicity prediction suggested that isolupalbigenin was less likely to cause hepatotoxicity or carcinogenicity, whereas pharmacokinetic prediction suggested that isolupalbigenin has high intestinal absorption with medium Caco2 permeability. In addition, isolupalbigenin was predicted to have a medium volume of distribution (Vd).

Conclusion: Isolupalbigenin isolated from the stem bark of with cytotoxic activity supports further development of plants from the genus as a medicinal plant for alternative therapy against cancer.