The discovery of novel openers of Ca2+-dependent large-conductance potassium channels: Pharmacophore search and physiological evaluation of flavonoids

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 mSlo expressed in Xenopus laevis oocytes. The cyclic constrained flavonoids were found to be more efficacious than the acyclic phloretin.