title: Flavonoids as vasorelaxant agents: synthesis, biological evaluation and quantitative structure activities relationship (QSAR) studies.
abstract: A series of 2-(2-diethylamino)-ethoxychalcone and 6-prenyl(or its isomers)-flavanones 10a,b and 11a-g were synthesized and evaluated for their vasorelaxant activities against rat aorta rings pretreated with 1 μM phenylephrine (PE). Several compounds showed potent vasorelaxant activities. Compound 10a (EC(50) = 7.6 μM, E(max) = 93.1%), the most potent one, would be a promising structural template for development of novel and more efficient vasodilators. Further, 2D-QSAR analysis of compounds 10a,b and 11c-e as well as thirty previously synthesized flavonoids 1-3 and 12-38 using Enhanced Replacement Method-Multiple Linear Regression (ERM-MLR) was further performed based on an optimal set of molecular descriptors (H5m, SIC2, DISPe, Mor03u and L3m), leading to a reliable model with good predictive ability (R(train)(2) = 0.839, Q(loo)(2) = 0.733 and R(test)(2) = 0.804). The results provide good insights into the structure- activity relationships of the target compounds.
authors.affiliation: ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China.
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Dong
authors.forename: Yanming
authors.initials: Y
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Peng
authors.initials: P
authors.lastname: Wu
authors.forename: Jiadi
authors.initials: J
authors.lastname: Gao
authors.forename: Jianchao
authors.initials: J
authors.lastname: Xu
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Yongzhou
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects*; D002478:Cells, Cultured; D047188:Chalcones / Q000138:chemical synthesis / Q000494:pharmacology; D005021:Ethylamines / Q000138:chemical synthesis / Q000494:pharmacology; D005419:Flavonoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D015394:Molecular Structure; D009924:Organ Culture Techniques; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: C570551:2-(2-diethylamino)-ethoxychalcone; D047188:Chalcones; D005021:Ethylamines; D005419:Flavonoids; D014665:Vasodilator Agents