Synthesis and Anti-Inflammatory Activities of Phloroglucinol-Based Derivatives.

The natural product phloroglucinol-based derivatives representing monoacyl-, diacyl-, dimeric acyl-, alkylated monoacyl-, and the nitrogen-containing alkylated monoacylphloro- glucinols were synthesized and evaluated for inhibitory activities against the inflammatory mediators such as inducible nitric oxide synthase (iNOS) and nuclear factor kappaB (NF-κB). The diacylphloroglucinol compound 2 and the alkylated acylphloroglucinol compound 4 inhibited iNOS with IC₅₀ values of 19.0 and 19.5 µM, respectively, and NF-κB with IC₅₀ values of 34.0 and 37.5 µM, respectively. These compounds may serve as leads for the synthesis of more potent anti-inflammatory compounds for future drug discovery.