Synthesis, anti-inflammatory activity, and conformational relationship studies of chromone derivatives incorporating amide groups

Abstract

Inflammation is the initial biological reaction of the immune system to various stimuli such as infection, injury, or irritation. Extensive research has demonstrated that a growing array of diseases are triggered by inflammatory mechanisms. Currently, anti-inflammatory drugs are widely utilized in clinical practice due to their therapeutic advantages; however, the potential side effects cannot be ignored by us. In our work, a series of amide compounds with chromones as the parent nucleus were designed and synthesized using the principle of colligated drug design. The results of the biological evaluation indicated that four compounds exhibited lower EC50 values compared to the positive drug ibuprofen. Notably, compound 5–9 showed optimal inhibitory activity (EC50 = 5.33 ± 0.57 μM) against the production of nitric oxide (NO) induced by lipopolysaccharide (LPS) in RAW264.7 cells. Structure-activity relationships (SAR) showed that the presence of electron-withdrawing groups at positions 5 and 8, or electron-donating groups at positions 6 and 7 of the parent nucleus of the chromones can enhance the anti-inflammatory activity of the chromones. The molecular docking studies predicted the mode of interaction between the compounds and protein. Additionally, these studies have demonstrated that the amide bond is the key radical to the anti-inflammatory effect. Based on the summary of the aforementioned studies, it can be inferred that compound 5–9 exhibit potential as an anti-inflammatory drug that deserves further investigation.