The Discovery of Novel Openers of Ca2+-Dependent Large-Conductance Potassium Channels: Pharmacophore Search and Physiological Evaluation of Flavonoids.

Abstract Three-dimensional database searching based on the pharmacophore model of the known maxi-K opener NS-004 ( 1 ) and electrophysiological evaluation led to the discovery of flavonoids ( 3c and 3d ) as openers of the cloned maxi-K channel m Slo expressed in Xenopus laevis oocytes. The cyclic constrained flavonoids were found to be more efficacious than the acyclic phloretin.