Pharmacokinetics and Metabolites of 12 Bioactive Polymethoxyflavones in Rat Plasma.

Polymethoxyflavones (PMFs) are a subgroup of flavonoids possessing various health benefits. 3,5,7,4'-Tetramethoxyflavone (), 5,6,7,4'-tetramethylflavone (), 3,7,3',4'-tetramethoxyflavone (), 5,7,3',4'-tetramethoxyflavone (), 5-hydroxy-3,7,2',4'-tetramethoxyflavone (), 3,5,7,2',4'-pentamethoxyflavone (), 5-hydroxy-3,7,3',4'-tetramethoxyflavone (), 3-hydroxy-5,7,3',4'-tetramethylflavone (), 3,5,7,3',4'-pentamethoxyflavone (), 5-hydroxy-3,7,3',4',5'-pentamethoxyflavone (), 3-hydroxy-5,7,3',4',5'-pentamethoxyflavone (), and 3,5,7,3',4',5'-hexamethoxylflavone () were 12 bioactive and available PMFs. The aim of this study was to investigate the pharmacokinetic, metabolite, and antitumor activities as well as the structure-pharmacokinetic-antitumor activity relationships of these 12 PMFs to facilitate further studies of their medicinal potentials. The cytotoxicity of PMFs with a hydroxy group toward HeLa, A549, HepG2, and HCT116 cancer cell lines was generally significantly more potent than that of PMFs without a hydroxy group. Compounds , , , , and were all undetectable in rat plasma, while compounds -, , , and were detectable. Both the number and position of hydroxy and methoxy groups played an important role in modulating PMF pharmacokinetics and metabolites.