title: α-glucosidase inhibitors from Brickellia cavanillesii.
abstract: An aqueous extract from the aerial parts of Brickellia cavanillesii attenuated postprandial hyperglycemia in diabetic mice during oral glucose and sucrose tolerance tests. Experimental type-II DM was achieved by treating mice with streptozotocin (100 mg/kg) and β-nicotinamide adenine dinucleotide (40 mg/kg). These pharmacological results demonstrated that B. cavanillesii is effective for controlling fasting and postprandial blood glucose levels in animal models. The same aqueous extract also showed potent inhibitory activity (IC(50) = 0.169 vs 1.12 mg/mL for acarbose) against yeast α-glucosidase. Bioassay-guided fractionation of the active extract using the α-glucosidase inhibitory assay led to the isolation of several compounds including two chromenes [6-acetyl-5-hydroxy-2,2-dimethyl-2H-chromene (1) and 6-hydroxyacetyl-5-hydroxy-2,2-dimethyl-2H-chromene (2)], two sesquiterpene lactones [caleins B (3) and C (4)], several flavonoids [acacetin (5), genkwanin (6), isorhamnetin (7), kaempferol (8), and quercetin (9)], and 3,5-di-O-caffeoylquinic acid (10). Chromene 2 is a new chemical entity. Compounds 2, 4, 7, and 9 inhibited the activity of yeast α-glucosidase with IC(50) 0.42, 0.28, 0.16, and 0.53 mM, respectively, vs 1.7 mM for acarbose. Kinetic analysis revealed that compounds 4 and 7 behaved as mixed-type inhibitors with K(i) values of 1.91 and 0.41 mM, respectively, while 2 was noncompetititive, with a K(i) of 0.13 mM. Docking analysis predicted that these compounds, except 2, bind to the enzyme at the catalytic site.
authors.affiliation: Facultad de Química,  Universidad Nacional Autónoma de México , México DF 04510, México.
authors.forename: Sonia
authors.initials: S
authors.lastname: Escandón-Rivera
authors.forename: Martin
authors.initials: M
authors.lastname: González-Andrade
authors.forename: Robert
authors.initials: R
authors.lastname: Bye
authors.forename: Edelmira
authors.initials: E
authors.lastname: Linares
authors.forename: Andrés
authors.initials: A
authors.lastname: Navarrete
authors.forename: Rachel
authors.initials: R
authors.lastname: Mata
mesh_terms: D000818:Animals; D019659:Asteraceae / Q000737:chemistry*; D001578:Benzopyrans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D065089:Glycoside Hydrolase Inhibitors; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008297:Male; D008800:Mexico; D051379:Mice; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013395:Sucrose / Q000008:administration & dosage; D000520:alpha-Glucosidases / Q000378:metabolism
chemical_list: C573867:6-hydroxyacetyl-5-hydroxy-2,2-dimethyl-2H-chromene; D001578:Benzopyrans; D001786:Blood Glucose; D005419:Flavonoids; D065089:Glycoside Hydrolase Inhibitors; D007783:Lactones; D012717:Sesquiterpenes; D013395:Sucrose; D000520:alpha-Glucosidases