title: Protoapigenone derivatives: albumin binding properties and effects on HepG2 cells.
abstract: Protoapigenone (Pa) is a flavone aglycone with a p-quinol structure in its B-ring. It was first discovered in Thelypteris torresiana, a native fern in Taiwan. Recent studies highlighted that protoapigenone and some of its derivatives show very potent anticancer activity against several types of tumors, using both in vitro and in vivo models. Despite the growing body of evidence on the selective anticancer potential of protoapigenone and its derivatives, no data are available on their pharmacokinetical properties. In our present research, albumin binding properties of Pa and seven different 1'-O-alkyl protoapigenone derivatives were analyzed as well as their biochemical effects on HepG2 tumor cell line in comparison with the flavone apigenin. Our results are in good accordance with the data of previous investigations of 1'-O-alkylated derivatives of protoapigenone (with the exception of isopropyl and allyl derivatives) showing similar or higher antitumor effects than Pa. Furthermore structural changes in Pa cause a very remarkable influence on plasma albumin binding affinity of the derivatives. Our investigation proves that parallel with changes of lipophilic character and extent of plasma protein binding properties of Pa derivatives a consequent alteration occurs in their pharmacokinetic behavior without losing the pharmacodynamic effect. Based on our study a better understanding of the structural and biochemical behavior of different chemically modified flavonoid derivatives could be achieved making further design of in vivo experiments feasible.
authors: Institute of Laboratory Medicine, University of Pécs, Pécs H-7624, Hungary.
authors: Miklós
authors: M
authors: Poór
authors: Yin
authors: Y
authors: Li
authors: Sándor
authors: S
authors: Kunsági-Máté
authors: Zsófia
authors: Z
authors: Varga
authors: Attila
authors: A
authors: Hunyadi
authors: Balázs
authors: B
authors: Dankó
authors: Fang-Rong
authors: FR
authors: Chang
authors: Yang-Chang
authors: YC
authors: Wu
authors: Tamás
authors: T
authors: Kőszegi
mesh_terms: D000418:Albumins / Q000737:chemistry / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003512:Cyclohexanones / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D047309:Flavones / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D011485:Protein Binding
chemical_list: D000418:Albumins; D000970:Antineoplastic Agents; D003512:Cyclohexanones; D047309:Flavones; C524112:protoapigenone