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.