Antioxidant and anti-inflammatory cembrane-type diterpenoid from Echinoidea sea urchin Stomopneustes variolaris attenuates pro-inflammatory 5-lipoxygenase

Abstract

Chemical investigation of pharmacologically active compounds from the Echinoidea sea urchin Stomopneustes variolaris resulted in the separation of an unreported cembrane type of diterpenoid, which was characterised as 4-hydroxy-1-(16-methoxyprop-16-en-15-yl)-8-methyl-21,22-dioxatricyclo[11.3.1.15,8]octadecane-3,19-dione by spectroscopic experiments. The compound exhibited greater inhibitory potential against inflammatory agent 5-lipoxygenase (IC50 2.01 mM) than that exhibited by synthetic ibuprofen (IC50 4.50 mM). The selectivity ratio of cyclooxygenase-1 to cyclooxygenase-2 for the studied compound was found to be greater (1.25) than that of ibuprofen (0.43), which could be accounted for the prospective anti-inflammatory property of the cembrane-type diterpenoid against inducible pro-inflammatory cyclooxygenase-2. Potent antioxidant activity of the studied compound was characterised by its greater scavenging effects on 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis-3-ethylbenzothiozoline-6-sulfonic acid radicals (IC50 1.41 and 1.61 mM, respectively) than the standard antioxidative agent α-tocopherol (IC50 1.51 and 1.70 mM, respectively). The greater electronic parameters (topological polar surface area of 82.06) together with two hydrogen bonded interactions at the active site of cyclooxygenase-2 and lesser binding energy (−8.91 kcal/mol) corroborated its prospective anti-inflammatory activity. Therefore, the presently studied cembrane-type diterpenoid could be utilised in medicinal formulations as an effective anti-inflammatory agent.