title: Docking and SAR studies of salacinol derivatives as alpha-glucosidase inhibitors.
abstract: Salacinol is a potent alpha-glucosidase inhibitor isolated from Salacia reticulata, and a good lead compound for an antidiabetic drug. It is essential to clarify the binding state of salacinol to alpha-glucosidase for efficient optimization study using structure-based drug design. Redocking simulations of two inhibitors, acarbose and casuarine whose complex structures are known, were performed to assure the appropriate docking pose prediction. The simulation reproduced both experimental binding states with accuracy. Then, using the same simulation protocol, the binding mode of salacinol and its derivatives has been predicted. Salacinol bound to the protein with a similar binding mode as casuarine, and the predicted structures could explain most of the structure-activity relationships of salacinol derivatives.
authors.affiliation: Faculty of Pharmacy, Kinki University, Higashi-osaka, Osaka 577-8502, Japan. nakas@phar.kindai.ac.jp
authors.forename: Shinya
authors.initials: S
authors.lastname: Nakamura
authors.forename: Kazunori
authors.initials: K
authors.lastname: Takahira
authors.forename: Genzoh
authors.initials: G
authors.lastname: Tanabe
authors.forename: Toshio
authors.initials: T
authors.lastname: Morikawa
authors.forename: Mika
authors.initials: M
authors.lastname: Sakano
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Ninomiya
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Muraoka
authors.forename: Isao
authors.initials: I
authors.lastname: Nakanishi
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors; D006860:Hydrogen Bonding; D049918:Salacia / Q000737:chemistry; D013329:Structure-Activity Relationship; D013402:Sugar Alcohols / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D013431:Sulfates / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D013816:Thermodynamics; D000520:alpha-Glucosidases / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D013402:Sugar Alcohols; D013431:Sulfates; C427963:salacinol; D000520:alpha-Glucosidases