# Chalcones inhibit firefly bioluminescence dependent on A and B-ring substitution pattern – a structure-activity study combined with molecular docking

## TL;DR

Some chalcone compounds can block firefly luciferase activity, which is important for reporter gene assays used in drug discovery.

## Contribution

The study reveals how structural changes in pyranochalcones affect their ability to inhibit firefly luciferase.

## Key findings

- Pyranochalcones inhibit firefly luciferase with IC50 values between 7.82 µM and 92.99 µM.
- Molecular docking suggests structural features determine selectivity for luciferase inhibition.
- Small structural modifications significantly alter inhibition levels, affecting reporter gene assay reliability.

## Abstract

Chalcones represent a privileged scaffold in medicinal chemistry, with pyranochalcones, featuring an additional chromane-like ring, identified as neurogenic and neuroprotective. Reporter gene assays, often used to study these and other effects, can produce false positives due to firefly luciferase stabilisation by inhibitors. The present study demonstrates that pyranochalcones inhibit firefly luciferase activity, with inhibition levels ranging from none to 100% and IC50 values of 7.82 µM to 92.99 µM. Furthermore, molecular docking offers potential structure-based explanations for the observed selectivity of compounds towards firefly luciferase inhibition. Even slight modifications in the molecular structure lead to significant changes in luciferase inhibition, underscoring the importance of these findings for understanding structure-activity relationships in reporter gene assays. Accordingly, caution is advised when using reporter gene assays based on firefly luciferase and pyranochalcones, as the IC50 values are within the range of concentrations commonly used in both in vivo and in vitro assays.