Cistobislactone, an undescribed variant of 14-membered bislactonic macrodiolide, from old-lady octopus (family Octopodidae) attenuates inflammatory lipoxygenase.

Chemical evaluation of specialised metabolites from the old-lady marine octopus (family Octopodidae) led to the isolation of an undescribed 14-membered bislactonic macrodiolide cistobislactone, which was characterized as 12-(4'-ethyl-6'-methoxy-3'-methyl-hex-1-enyl)-5,11-dihydroxy-6-methyl-1,7-dioxacyclotetradeca-3,9-diene-2,8-dione. Cistobislactone exhibited noticeably greater inhibitory potential against 5-lipoxygenase (IC 2.06 mM) compared to standard anti-inflammatory agent ibuprofen (IC 4.61 mM,  < 0.05). Superior antioxidant properties of cistobislactone against the oxidants (IC ∼1.8 mM) also reinforced its promising anti-inflammatory activity. Higher electronic properties (topological polar surface area of 102.3) and balanced hydrophobicity (logarithm of octanol-water coefficient ∼3) could recognize its higher interaction at the enzyme active site resulting in an effective attenuation of 5-lipoxygenase and efficient inter-membrane permeability. Comparatively lesser binding energy (-6.5 kcal mol) and docking score (-7.5 kcal mol) of cistobislactone with the aminoacyl residues of 5-lipoxygenase could further recognize its anti-inflammatory potential.