Anti-Inflammatory Activity of Geldanamycin and Its Derivatives in LPS-Induced RAW 264.7 Cells

Abstract

Geldanamycin (1) had been isolated as a major compound from Streptomyces zerumbet W14; an endophyte of Zingiber zerumbet (L.) Smith. Two new geldanamycin derivatives; 17-(tryptamine)-17-demethoxygeldanamycin (2) and 17-(5'-methoxytryptamine)-17-demethoxygeldanamycin (3) were synthesized and their anti-inflammatory activity was evaluated in LPS-induced macrophage RAW 264.7 cells by investigating their effects on the inhibition of production of NO, PGE 2 , TNF-α, IL-1β, IL-6 and IL-10. The data obtained were consistent with the modulation of TNF-α, IL-1β, IL-6, IL-10 production by these derivatives at concentration of 1 to 5 µg/ml. A similar effect was also observed when LPS-induced NO release and PGE 2 production were tested. The inhibitory effects were shown in concentration-dependent manners. From the obtained results, it was concluded that two new geldanamycin derivatives possess anti-inflammatory activity on LPS-induced RAW 264.7 cells. They could be useful for the management of inflammatory diseases.