The impact of B-ring substituents on the styrylchromones' ability to modulate the levels of reactive prooxidant species

Reactive oxygen and nitrogen species (ROS and RNS), at normal physiological levels, play an important role in the normal functioning of the body. However, during the inflammatory process, there is an increase in their production, especially by neutrophils - oxidative burst. 2-Styrylchromones (2-SC), a group of chromones featuring a styryl moiety attached at C-2 of the chromone core, have demonstrated anti-inflammatory potential. Nevertheless, there are no reports about their effect on human neutrophils’ viability and oxidative burst.

In this study we evaluated the impact of nine structurally related 2-SC on the neutrophils’ viability and modulation of oxidative burst, applying fluorometric and chemiluminescent methodologies, respectively.

Considering the substituents present on B-ring, 2-SC were divided into groups: group A, with OH groups; group B, with OCH₃ groups and group C, with OBn groups. None of the 2-SC affected neutrophils’ viability, up to the maximum tested concentration. 2-SC from group A were the most effective modulators of neutrophils’ oxidative burst (IC₅₀ ≈ 1 μM).

In conclusion, the type of substituents on B-ring, especially a catechol group, influence the levels of ROS and RNS resulting from neutrophils’ oxidative burst. This work reinforces the 2-SC scaffold potential as anti-inflammatory drugs.

Acknowledgments: The work was supported through the project UIDB/50006/2020, funded by FCT/MCTES through national funds, and from the European Union (FEDER funds through COMPETE POCI-01-0145-FEDER-029253). Mariana Lucas thanks FCT for her PhD grant (2021.06746.BD). Marisa Freitas acknowledges her contract under the CEEC Individual (2020.04126.CEECIND/CP1596/CT0006).