Synthesis and Biological Properties of Pyranocoumarin Derivatives as Potent Anti-Inflammatory Agents

Abstract

This study aimed to synthesize 23 coumarin derivatives and analyze their anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophages. A cytotoxicity test performed on LPS-induced RAW264.7 macrophages revealed that none of the 23 coumarin derivatives were cytotoxic. Among the 23 coumarin derivatives, coumarin derivative 2 showed the highest anti-inflammatory activity by significantly reducing nitric oxide production in a concentration-dependent manner. Coumarin derivative 2 inhibited the production of proinflammatory cytokines, including tumor necrosis factor alpha and interleukin-6, and decreased the expression level of each mRNA. In addition, it inhibited the phosphorylation of extracellular signal-regulated kinase, p38, c-Jun NH2-terminal kinase, nuclear factor kappa-B p65 (NF-κB p65), and inducible nitric oxide synthase. These results indicated that coumarin derivative 2 inhibited LPS-induced mitogen-activated protein kinase and NF-κB p65 signal transduction pathways in RAW264.7 cells, as well as proinflammatory cytokines and enzymes related to inflammatory responses, to exert anti-inflammatory effects. Coumarin derivative 2 showed potential for further development as an anti-inflammatory drug for the treatment of acute and chronic inflammatory diseases.

The molecular effects underlying the pharmacological activities of daphnetin

“…All six types comprise a coumarin moiety and exert diverse medical functions via their distinct structural characteristics. Therefore, coumarins have been widely used in complementary and alternative medicine owing to their potent and comprehensive pharmacological activities, including anti-inflammatory ( Min et al, 2023 ), antibacterial ( Zeng et al, 2023 ), antiviral ( Hwu et al, 2022 ), antioxidant ( Sultana et al, 2022 ), anti-Alzheimer’s Disease (AD) ( Liu W. et al, 2022 ), and antitumor effects ( Ahmed et al, 2022 ). Based on this, a variety of derivative drugs containing a coumarin moiety have been developed and used in clinics, such as esculetin, phenprocoumon, warfarin, acenocoumarol, hymecromone, carbochromen, dicoumarol, and daphnetin ( Figure 1 ).…”