Vasorelaxant effect of flavonoids through calmodulin inhibition: Ex vivo, in vitro, and in silico approaches.
In our search for potential antihypertensive agents, a series of structurally-related flavonoids was screened. Ex vivo and in vitro biological evaluations indicated that compounds 1-7 displayed an important vasorelaxant effect on the endothelium-intact (E(+)) and -denuded (E(-)) aortic rings test. Their in vitro anti-calmodulin (CaM) properties were determined by means of the inhibitory effect on the activation of the calmodulin-sensitive cAMP phosphodiesterase (PDE1) assay. Molecular modeling experiments were also performed in order to explore the probable binding site of 1-7 with CaM, and the results indicated that they could bind to the protein in the same pocket as trifluoperazine (TFP), a well-known CaM inhibitor.
Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62209, Mexico.
Mariana
M
Torres-Piedra
Mario
M
Figueroa
Oswaldo
O
Hernández-Abreu
Maximiliano
M
Ibarra-Barajas
Gabriel
G
Navarrete-Vázquez
Samuel
S
Estrada-Soto
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D008958:Models, Molecular; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000737:chemistry / Q000494:pharmacology*
D002147:Calmodulin; D005419:Flavonoids; D014665:Vasodilator Agents