Synthesis and anti-inflammatory activity of novel triazole hybrids of (+)-usnic acid, the major dibenzofuran metabolite of the lichen Usnea longissima

摘要

(+)-Usnic acid ((R)-2,6-diacetyl-7,9-dihydroxy8,9b- dimethyl-1,3(2H, 9bH)-dibenzo-furandione), a diben-zofuran isolated from the lichen Usnea longissima, has been chemically transformed to synthesize a series of sixteen novel triazole analogs by click chemistry approach. The synthesized compounds were tested for their anti-inflammatory potential against the cytokines TNF-alpha and IL-1 beta in U937 cell lines. The bromo enamines (2a, 2b), azido enamines (3a, 3b) and triazole analogs (4f, 4g, 4h, 5f, 5g and 5h) exhibited promising anti-inflammatory activity against TNF-alpha with IC50 values ranging from 1.40 to 5.70 mu M. Most significantly, the IC50 values of compounds 5f (1.40 mu M) and 5h (1.88 mu M) are the lowest among the compounds tested and found close to that of standard prednisolone. Hence, these two compounds can be considered as lead molecules for further fine tuning to make highly potent anti-inflammatory therapeutic agents.