Thiazolo-pyrones as potential anti-inflammatory agents

A series of chiral thiazolo-pyrones were designed and synthesized to explore their potential as anti-inflammatory agents. These compounds were evaluated for their ability to inhibit inflammation both in vitro and in vivo. In vitro studies, most of the compounds exhibited potent inhibition of LPS-induced nitric oxide (NO) releasing in RAW264.7 cells with limited cytotoxicity. In particular, compound 3n displayed the most potent inhibitory activity. It reduced NO production by 95.2 % at a concentration of 30 μM. It also suppressed prostaglandin E2 (PGE₂) release both at the cellular level (IC₅₀ 16.06 μM) and enzyme level (IC₅₀ 0.72 μM) in a dose-dependent manner. Compound 3n also displayed TNF-α and IL-6 inhibition potency. To elucidate the underlying mechanisms, Western blot was performed and it showed that 3n effectively down-regulated the expression of iNOS and COX-2, key enzymes involved in NO and PGE₂ production. Activation of the MAPK signaling pathway was also inhibited, which was supported by the decreased phosphorylation of p38, ERK, and JNK. To assess the in vivo activity of 3n, a xylene-induced mice ear edema model was employed. Treatment with 3n obviously relieved the swelling ear of the mice in a dose-dependent manner. These findings highlights the potential of thiazolo-pyrones being promising anti-inflammatory agents for disorders characterized by NO and COX-2 overproduction.