Site selective synthesis and anti-inflammatory evaluation of Spiro-isoxazoline stitched adducts of arteannuin B

Spiroisoxazoline analogues of arteannuin B were synthesized through 1, 3-dipolar cycloaddition of arteannuin B with aryl nitrile oxides and screened for anti-inflammatory activity in RAW 264.7 macrophage cells. Among all 8i, 8m and 8n were most potent for IL-6, TNF-α, and LPS induced nitric oxide production in RAW 264.7 cells than the parent compound. [Display omitted] •Synthesis of spiro-isoxazoline analogues of arteannuin B (1) with aryl nitrile oxides 7.•Compounds 8i, 8m and 8n were most potent of cytokines IL-6 with IC50 1.5, 0.17, 0.56 µM.•Compounds 8i, 8m and 8n potent inhibition of NO with IC50 value 0.3, 0.09, 0.2 µM. A library of new spiroisoxazoline analogues of arteannuin B was synthesized through 1, 3-dipolar cycloaddition in stereoselective fashion and consequently screened for anti-inflammatory activity in RAW 264.7 macrophage cells. Three potent analogues (8i, 8 m, and 8n) were found to attenuate the LPS induced release of cytokines IL-6 and TNF-α more potently than the parent molecule. Also, the inhibition of LPS induced nitric oxide production in these cells show moderate to high efficacy. None of the three potent molecules have altered the viability of RAW 264.7 cells following 48 h incubation suggesting that the inhibition of cytokines and nitric oxide production exhibited in the cells was not due to toxicity. In addition, these compounds exhibit an IC50 range of 0.17 µM-1.57 µM and 0.09 µM-0.35 µM for the inhibition of IL-6 release and nitric oxide production respectively. The results disclose potent inhibition of pro-inflammatory mediators which are encouraging and warrant further investigations to develop new therapeutic agents for inflammatory diseases.