-Ketoheterocycles Able to Inhibit the Generation of Prostaglandin E₂ (PGE₂) in Rat Mesangial Cells

Prostaglandin E-2 (PGE(2)) is a key mediator of inflammation, and consequently huge efforts have been devoted to the development of novel agents able to regulate its formation. In this work, we present the synthesis of various alpha-ketoheterocycles and a study of their ability to inhibit the formation of PGE(2) at a cellular level. A series of alpha-ketobenzothiazoles, alpha-ketobenzoxazoles, alpha-ketobenzimidazoles, and alpha-keto-1,2,4-oxadiazoles were synthesized and chemically characterized. Evaluation of their ability to suppress the generation of PGE(2) in interleukin-1 beta plus forskolin-stimulated mesangial cells led to the identification of one alpha-ketobenzothiazole (GK181) and one alpha-ketobenzoxazole (GK491), which are able to suppress the PGE(2) generation at a nanomolar level.