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

Chemical evaluation of specialised metabolites from the old-lady marine octopus Cistopus indicus (family Octopodidae) led to the isolation of an undescribed 14-membered bislactonic macrodio-lide cistobislactone, which was characterized as 12-(4’-ethyl-6’- methoxy-3’-methyl-hex-1-enyl)-5,11-dihydroxy-6-methyl-1,7-dioxa-cyclotetradeca-3,9-diene-2,8-dione. Cistobislactone exhibited noticeably greater inhibitory potential against 5-lipoxygenase (IC50 2.06 mM) compared to standard anti-inflammatory agent ibupro-fen (IC50 4.61 mM, p < 0.05). Superior antioxidant properties of cis-tobislactone against the oxidants (IC50 -1.8 mM) also reinforced its promising anti-inflammatory activity. Higher electronic proper-ties (topological polar surface area of 102.3) and balanced hydro-phobicity (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-1 ) and docking score (-7.5 kcal mol-1 ) of cistobislac-tone with the aminoacyl residues of 5-lipoxygenase could further recognize its anti-inflammatory potential.