title: Role of the side chain stereochemistry in the α-glucosidase inhibitory activity of kotalanol, a potent natural α-glucosidase inhibitor. Part 2.
abstract: To examine the role of the side chain of kotalanol (2), a potent natural α-glucosidase inhibitor isolated from Salacia reticulata, on inhibitory activity, four diastereomers (11a-11d) with reversed configuration (S) at the C-4' position in the side chain were synthesized and evaluated. Two of the four (11b and 11d) significantly lost their inhibitory activity against both maltase and sucrase, while the other two (11a and 11c) sustained the inhibitory activity to a considerable extent, showing distinct activity in response to the change of stereochemistry of the hydroxyls at the 5'and 6' positions. Different activities were rationalized with reference to in silico docking studies on these inhibitors with hNtMGAM. Against isomaltase, all four analogs showed potent inhibitory activity as well as 2, and 11b and 11d exhibited enzyme selectivity.
authors.affiliation: School of Pharmacy, Kinki University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan.
authors.forename: Genzoh
authors.initials: G
authors.lastname: Tanabe
authors.forename: Kanjyun
authors.initials: K
authors.lastname: Matsuoka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yoshinaga
authors.forename: Weijia
authors.initials: W
authors.lastname: Xie
authors.forename: Nozomi
authors.initials: N
authors.lastname: Tsutsui
authors.forename: Mumen F
authors.initials: MF
authors.lastname: A Amer
authors.forename: Shinya
authors.initials: S
authors.lastname: Nakamura
authors.forename: Isao
authors.initials: I
authors.lastname: Nakanishi
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wu
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Muraoka
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D065089:Glycoside Hydrolase Inhibitors; D008958:Models, Molecular; D008968:Molecular Conformation; D009005:Monosaccharides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D049918:Salacia / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013431:Sulfates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000520:alpha-Glucosidases / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; C114502:Kotalanol; D009005:Monosaccharides; D013431:Sulfates; D000520:alpha-Glucosidases