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

ABSTRACT

(+)-Usnic acid ((R)-2,6-diacetyl-7,9-dihydroxy-8,9b-dimethyl-1,3(2H,9bH)-dibenzo-furandione), a dibenzofuran 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-[Formula see text] and IL-1[Formula see text] 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-[Formula see text] with [Formula see text] values ranging from 1.40 to 5.70 [Formula see text]M. Most significantly, the [Formula see text] values of compounds 5f (1.40 [Formula see text]M) and 5h (1.88 [Formula see text]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.