Phenanthrene and dihydrophenanthrene derivatives from Vanda curvifolia with cytotoxic activity against glioblastoma cells

Glioblastoma remains one of the most lethal and therapeutically intractable primary brain malignancies, with a critical need for novel therapeutic discoveries. Phenanthrenes and dihydrophenanthrenes, gaining attention for their cytotoxic and antiproliferative activities, represent a promising yet underexplored chemical space for glioblastoma drug discovery. Phytochemical investigation of Vanda curvifolia , a species of phenanthrene-rich family Orchidaceae, afforded ten previously undescribed phenanthrene and dihydrophenanthrene constituents, designated vandafolin A –J ( 1−10 ), together with twelve known compounds. Structures were elucidated by NMR and HR-ESI-MS, with absolute configurations assigned by ECD spectroscopy and optical rotation measurements supported by TDDFT calculations. Vandafolin A, B, G, and H exhibited moderate cytotoxicity against U-87 MG glioblastoma cells, while vandafolin A, G, and H further demonstrated moderate antiproliferative activity. Vandafolin A induced G0/G1 cell cycle arrest, while vandafolin G and H induced apoptosis in U-87 MG glioblastoma cells, as determined by propidium iodide (PI) and Annexin V/PI staining flow cytometry, respectively. These results identified vandafolin A, G, and H as preliminary cytotoxic hits against glioblastoma cells, warranting further mechanistic and structural investigation.