title: Molecular docking studies of phlorotannins from Eisenia bicyclis with BACE1 inhibitory activity.
abstract: In our consecutive research on an anti-AD remedy derived from maritime plants, the BACE1 inhibitory activities of Eisenia bicyclis and its isolated phlorotannins were evaluated. The E. bicyclis extract and its fractions exhibited predominant BACE1 inhibition. With the exception of phloroglucinol (1), all test phlorotannins isolated from the most active EtOAc soluble fraction, showed significant and non-competitive inhibition against BACE1:dioxinodehydroeckol (2, IC(50)=5.35 microM; K(i)=8.0); eckol (3, IC(50)=12.20 microM; K(i)=13.9); phlorofurofucoeckol-A (4, IC(50)=2.13muM; K(i)=1.3); dieckol (5, IC(50)=2.21 microM; K(i)=1.5); triphloroethol A (6, IC(50)=11.68 microM; K(i)=12.1); 7-phloroethol (7, IC(50)=8.59 microM; K(i)=7.2). In addition, plausible protein-ligand interactions of 3, 4, and 5 were similar and may occur primarily through the TYR132 and THR133 of BACE1 via molecular docking simulations (autodock 4.0 and fred 2.0 programs). As a result, the E. bicyclis extract and the phlorotannins contained therein would clearly have beneficial use in the development of therapeutic and preventive agents for AD and suggest potential guidelines for the design of BACE-selective inhibitors.
authors.affiliation: Division of Food Science and Biotechnology, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Jung
authors.forename: Sang Ho
authors.initials: SH
authors.lastname: Oh
authors.forename: Jae Sue
authors.initials: JS
authors.lastname: Choi
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D007700:Kinetics; D008958:Models, Molecular; D013634:Tannins / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D013634:Tannins; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human