Cytotoxicity and Molecular Docking to Histone Deacetylase of Phytochemicals from Ventilago denticulata Leaves

Phytochemical investigation of the ethyl acetate and methanol extracts of Ventilago denticulata leaves resulted in the isolation of five flavonoids (1-5) and three anthraquinones (6-8). Their structures were characterized using spectroscopic techniques including UV, IR, 1H NMR, 13C NMR, and 2D NMR, as well as mass spectrometry (MS). Among these, compounds 4 (rhamnetin) and 6 (frangulin B) emerged as potential HDAC inhibitors, displaying significant inhibitory activities against HeLa nuclear extract. Molecular docking with HDAC isoforms revealed their affinity, particularly for class II HDAC4 enzyme. Both compounds exhibited promising physicochemical properties compliant with Lipinski’s rule of five, indicative of their drug-like potential. In vitro antiproliferative assays demonstrated that compound 6 exhibited superior activity against HeLa, A549 and MCF-7 cancer cell lines with the IC50 values ranging from 8.35 to 20.93 mM, whereas compound 4 showed reduced cytotoxicity in non-cancerous Vero cells. Furthermore, compound 6 was isolated from V. denticulata for the first time.