The chemical constituents of xanthones from Calophyllum membranaceum and their cytochrome P450 family 1 enzymes inhibitory activities

The 95% ethanol extract from the dried stems and leaves of Calophyllum membranaceum Gardn. et Champ. was investigated for its chemical constituents using a combination of normal-phase silica gel column chromatography, reversed-phase silica gel column chromatography, and semi-preparative HPLC. Structural elucidation was accomplished by NMR spectroscopy and MS analysis, together with comparison with literature data, leading to the isolation and identification of 22 simple xanthones. Screening for inhibitory activity against CYP1 family enzymes revealed that 4-methoxyxanthone (4), 1,2-dimethoxyxanthone (9), and 1,5-dihydroxy-2,3-dimethoxyxanthone (21) selectively inhibited CYP1A2, with inhibition rates of (43.00±0.81)%, (60.60±3.26)%, and (43.00±3.69)%, respectively. In addition, 1,3,5-trihydroxyxanthone (12) selectively targeted CYP1A1, with an inhibition rate of (37.85±3.09)%. Molecular docking results indicated that these active compounds exhibited favorable binding affinity toward the corresponding target proteins of the CYP1 family and could form relatively stable interactions with relevant amino acid residues through hydrogen bonding.