Design, Synthesis, and Evaluation of Kirenol Derivatives as MMP‐8 Inhibitors with Anti‐inflammatory Activity

Abstract

The diterpene kirenol has notable biological activity. In this study, molecular docking software (Discovery Studio) was adopted to investigate the anti‐inflammatory and antioxidant properties of kirenol. Twenty‐nine kirenol derivatives were synthesized based on the molecular docking outcomes. Cytotoxicity analyses of the kirenol derivatives were performed in Raw264.7 macrophages using the CCK‐8 assay, and nitric oxide (NO) concentrations were determined using the Griess assay. The DCFH‐DA approach identified the general pattern of reactive oxygen species (ROS) fluctuations. The mitochondrial mass and morphology were detected using the Mito‐Tracker Red fluorescent probe. Preliminary bioassay tests indicated that the concentration of NO was substantially reduced by certain derivatives. Moreover, these derivatives inhibited LPS‐induced ROS generation, and one of them exhibited a further reducing ROS generation and pro‐inflammatory response by suppressing excessive mitochondrial fission. These findings suggest that this particular derivative may be a promising natural compound for combating oxidative inflammatory diseases.