First report of spiro-compounds from marine macroalga : prospective natural anti-inflammatory agents attenuate 5-lipoxygenase and cyclooxygenase-2.

The inflammation pathology is an orchestrated biological process and the dual inhibition of pro-inflammatory enzymes 5-lipoxygenase and cyclooxygenase-2 has been found to be an effective approach against inflammation. This study involves the characterisation of two previously undescribed spiro[5.5]undecanes, 3-(hydroxymethyl)-7-(methoxymethyl)-3,11-dimethyl-9-oxospiro[5.5]undec-4-en-10-methylbutanoate () and 4-ethoxy-11,11-dimethyl-7-methylene-8-(propionyloxy)spiro[5.5]undec-2-en-10,10-dihydroxytetrahydro-2-pyran-10-carboxylate () with potential anti-inflammatory properties, from seaweed by extensive-spectroscopic-experiments. These metabolites recorded prospective bioactivities against 5-lipoxygenase (IC < 2.80 mM), whereas their selectivity indices were significantly greater (∼1) than ibuprofen (0.89) ( < 0.05), which attributed selective anti-inflammatory potencies of the studied spiro[5.5]undecane derivatives against inducible cyclooxygenase-2 than constitutive cyclooxygenase-1. Radical scavenging potential of spiro[5.5]undec-2-en-10,10-dihydroxytetrahydro-2-pyran-10-carboxylate analogue () against oxidants, 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis-3 ethylbenzothiozoline-6-sulfonic acid were found to be greater (IC < 1.25 mM) than commercial standard, -tocopherol (IC 1.42-1.79 mM). The greater hydrogen-bonding interactions and binding affinity of (-10.13 kcal/mol) with 5-LOX appropriately corroborated its prospective anti-inflammatory activity.