Figure 3
From: A combinatorial approach for the discovery of cytochrome P450 2D6 inhibitors from nature
Workflow for the identification of novel CYP2D6 inhibitors in the 2D- natural products database: The starting points for the combinatorial workflow of in silico (blue) and in vitro (red) methods were 2D-databases that consisted of the chemical structure of natural products (1). Discovery Studio software was used to create (2) and virtually screen the 3D-databases for potential CYP2D6 inhibitors in silico (3). We selected those candidates for which no CYP2D6 inhibition data were available according to literature research (4). To investigate the inhibitory effect of the prospective inhibitors on CYP2D6 in vitro, a luminescence-based high-throughput assay was performed (5), including control reactions to avoid unspecific signals and thus false positive hits. In a last step, the confirmed inhibitors were docked in silico in the active site cavity to predict the binding pose and to estimate their ability to act as competitive inhibitors (6).
