title: Structure-activity relationship of wedelolactone analogues: structural requirements for inhibition of Na+, K+ -ATPase and binding to the central benzodiazepine receptor.
abstract: Coumestans 2a-i, bearing different patterns of substitution in A- and D-rings, were synthesized and evaluated as inhibitors of kidney Na+, K+ -ATPase and ligands for the central benzodiazepine (BZP) receptor. The presence of a hydroxyl group in position 2 favours the effect on Na+, K+ -ATPase but decreases the affinity for the BZP receptor, allowing the design of more selective molecules than the natural wedelolactone. On the other hand, the presence of a catechol in ring D is important for the effect on both molecular targets.
authors.affiliation: Departamento de Farmacologia Básica e Clínica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, RJ 21941-590, Brazil.
authors.forename: Elisa S C
authors.initials: ES
authors.lastname: Pôças
authors.forename: Daniele V S
authors.initials: DV
authors.lastname: Lopes
authors.forename: Alcides J M
authors.initials: AJ
authors.lastname: da Silva
authors.forename: Paulo H C
authors.initials: PH
authors.lastname: Pimenta
authors.forename: Fernanda B
authors.initials: FB
authors.lastname: Leitão
authors.forename: Chaquip D
authors.initials: CD
authors.lastname: Netto
authors.forename: Camilla D
authors.initials: CD
authors.lastname: Buarque
authors.forename: Flávia V
authors.initials: FV
authors.lastname: Brito
authors.forename: Paulo R R
authors.initials: PR
authors.lastname: Costa
authors.forename: François
authors.initials: F
authors.lastname: Noël
mesh_terms: D002396:Catechols / Q000737:chemistry / Q000494:pharmacology; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry; D006801:Humans; D007668:Kidney / Q000201:enzymology; D008024:Ligands; D011485:Protein Binding; D011963:Receptors, GABA-A / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D002396:Catechols; D003374:Coumarins; D004791:Enzyme Inhibitors; D008024:Ligands; D011963:Receptors, GABA-A; C051122:wedelolactone; D000254:Sodium-Potassium-Exchanging ATPase; C505898:coumestan