Andrographolide and its derivatives as TNF-alpha antagonists

摘要

The present invention relates to andrographolide and its derivatives of the general formula (I), as well as the stereoisomers and salts of andrographolide and the derivatives. Andrographolide and its derivatives represented by general formula (I) defined above are useful as TNFalpha (tumor necrosis factor alpha) antagonists or inhibitors which have inhibitory effect on the binding of TNFalpha to TNF-RI. Andrographolide exhibited inhibitor activity with IC₅₀ values 60 muM on L929 cell proliferation/cytotoxicity assay without cell cytotoxicity. In addition, in the animal model test of collagen-induced arthritis, andrographolide exhibited 50% paw edema. Andrographolide and its derivatives are promising sources with high TNFalpha-inhibiting or antagonizing activity.