Cytotoxic phenanthrene and racemosol derivatives from Bauhinia malabarica roots: network pharmacology and in silico mechanistic insights.

Phytochemical investigation of the roots of Bauhinia malabarica led to the isolation of ten compounds, including three previously unreported phenanthrene and racemosol derivatives, malathrene A, a rare phenanthrene derivative featuring an unprecedented C-1'-O-C-4 ether bridge, malasol A, and bauhinol B, together with an unreported natural product racemosol derivative, 9-O-methylracemosol, and six known compounds. Their structures were elucidated by spectroscopic methods, including IR, 1D and 2D NMR, and mass spectrometry, while the absolute configurations of malasol A and 9-O-methylracemosol were determined by electronic circular dichroism. Biological evaluation revealed that racemosol exhibited the most potent cytotoxic activity against HeLa cells (IC50 = 4.51 μM) and induced apoptosis in a dose-dependent manner. Network pharmacology analysis suggested that its cytotoxic effect is associated with modulation of multiple signaling pathways, particularly PI3K-Akt and MAPK pathways. Molecular docking indicated that racemosol interacts with the ATP-binding site of the EGFR kinase domain, supporting its potential role as a tyrosine kinase inhibitor. These findings expand the chemical diversity of racemosol-related natural products and highlight racemosol as a promising lead compound for future pharmacological studies.