Stomopnolides A-B from echinoidea sea urchin Stomopneustes variolaris: prospective natural anti-inflammatory leads attenuate pro-inflammatory 5-lipoxygenase

Two fourteen-membered macrocyclic pyrone derivatives named as stomopnolides were identified from the organic extract of echinoidea sea urchin Stomopneustes variolaris by extensive chromatographic purification, and were characterised as methyl 10-butyl-4a-methyl-2-oxo-octahydro-2H-cyclodeca[b]pyran-8-carboxylate (stomopnolide A) and methyl 8(2)-(4a-methyl-10-(10(2)-methylbutyl)-2-oxo-octahydro-2H-cyclodeca[b]pyran-8-yl)acetate (stomopnolide B) by spectroscopic methods. The macrocyclic pyrone derivative bearing pyran-8-carboxylate moiety (stomopnolide A) exhibited significantly greater antioxidant properties against 2,2-diphenyl-1-picrylhydrazyl (IC50DPPH 1.43 mM) and 2,2 '-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (IC(50)ABTS(+) 1.63 mM) free radicals than stomopnolide B (IC50 > 1.85 mM) and the commercial standard alpha-tocopherol (IC50 1.51 mM). Stomopnolide A exhibited potential attenuation property against pro-inflammatory 5-lipoxygenase (IC50 2.78 mM) than those exhibited by stomopnolide B (IC50 3.09 mM) and non-steroidal anti-inflammatory drug, ibuprofen (IC50 4.50 mM, p < 0.05), which signified the prospective anti-inflammatory activity of the former. The greater electronic parameters of stomopnolide A, along with greater number of hydrogen bonds and docking score obtained from the molecular docking studies attributed its potential anti-inflammatory activity.