Discovery of a novel general anesthetic chemotype using high-throughput screening.

ABSTRACT:

Background

The development of novel anesthetics has historically been a process of combined serendipity and empiricism, with most recent new anesthetics developed via modification of existing anesthetic structures.

Methods

Using a novel high-throughput screen employing the fluorescent anesthetic 1-aminoanthracene and apoferritin as a surrogate for on-pathway anesthetic protein target(s), we screened a 350,000 compound library for competition with 1-aminoanthracene-apoferritin binding. Hit compounds meeting structural criteria had their binding affinities for apoferritin quantified with isothermal titration calorimetry and were tested for γ-aminobutyric acid type A receptor binding using a flunitrazepam binding assay. Chemotypes with a strong presence in the top 700 and exhib

SUBMITTER: McKinstry-Wu AR 

PROVIDER: S-EPMC4300529 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature