COX-2 inhibitory activity of cafestol and analogs from coffee beans

Abstract

Two kaurane diterpenes, namely cafestol (1) and kahweol (2), were isolated from hydrolyzed fraction of the fixed oil of Ethiopian Coffea arabica unroasted beans, using AgNO3-impregnated silica gel chromatography. In addition, cafestol palmitate (3) and kahweol palmitate (4), the two natural diterpene esters of C. arabica, were also synthesized. Compounds 1-4 were evaluated for anti-inflammatory activity using cyclooxygenase-2 (COX-2), cell aggregation, cell proliferation, cell adhesion, iNOS and antioxidant assays. The COX-2 inhibitory activity of cafestol (1) was found to be 20-fold more potent than kahweol (2) (IC50 value 0.25 μg/mL vs. 5.0 μg/mL), while compounds 3 and 4 were weakly active. The isolation and structure elucidation of the diterpenes 1 and 2, preparation of compounds 3 and 4, and their biological activities are presented in this paper.