title: β(2)-Adrenergic activity of 6-methoxykaempferol-3-O-glucoside on rat uterus: in vitro and in silico studies.
abstract: 6-Methoxykaempferol-3-O-glucoside (6-MKG) was isolated from a Sudanese herb (El-hazha). The pharmacological effects of 6-MKG were tested on isolated non-pregnant or late-pregnant rat uteri in vitro, whilst docking studies were carried out modelling of the binding of 6-MKG to the rat β(2)-adrenoceptor in silico. In vitro studies revealed that 6-MKG was able to relax both the non-pregnant and the late-pregnant uterine contractility with 50% of the E(max) of terbutaline, whilst the EC(50) for 6-MKG was at least half than that of terbutaline. The β(2)-adrenoceptors antagonist 3-(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]butan-2-ol(ICI118,551) competitively antagonised the relaxing effect of 6-MKG. Radioligand binding and cAMP studies confirmed the β(2)-adrenoceptors agonistic property of the compound. In in silico docking studies, 6-MKG bound to rat β(2)-adrenoceptors with low ∆G(bind) value (-11.53±0.06 kcal/mol) and it interacted with four residues of the active site (Asp(113), Asn(312), Cys(191)and Tyr(316)). It is concluded that 6-MKG exerts weak β(2)-adrenoceptor agonistic activity and can be considered a natural compound with potential therapeutic significance in the field of premature pregnant uterine contractions and asthmatic problems.
authors.affiliation: Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, H-6720 Szeged, Eötvös u. 6, Hungary.
authors.forename: Aimun A E
authors.initials: AA
authors.lastname: Ahmed
authors.forename: Arpad
authors.initials: A
authors.lastname: Marki
authors.forename: Robert
authors.initials: R
authors.lastname: Gaspar
authors.forename: Andrea
authors.initials: A
authors.lastname: Vasas
authors.forename: M M E
authors.initials: MM
authors.lastname: Mudawi
authors.forename: Judit
authors.initials: J
authors.lastname: Verli
authors.forename: Balázs
authors.initials: B
authors.lastname: Jójárt
authors.forename: Judit
authors.initials: J
authors.lastname: Hohmann
authors.forename: George
authors.initials: G
authors.lastname: Falkay
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000378:metabolism / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D019295:Computational Biology; D005260:Female; D005960:Glucosides / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D044949:Kaempferols / Q000378:metabolism / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009126:Muscle Relaxation / Q000187:drug effects; D011247:Pregnancy; D011487:Protein Conformation; D051381:Rats; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*
chemical_list: C568814:6-methoxykaempferol-3-O-glucoside; D058666:Adrenergic beta-2 Receptor Agonists; D005960:Glucosides; D044949:Kaempferols; D008024:Ligands; D018343:Receptors, Adrenergic, beta-2