Cistobislactones A-B, two sixteen-membered spiro-linked macrocylic bislactones from marine octopus Cistopus indicus: new anti-inflammatory agents attenuate arachidonate 5-lipoxygenase

Biochemical analysis of secondary metabolites of marine old-woman octopus Cistopus indicus (family Octopodidae) led to the identification of two sixteen-membered spiro-linked macrocyclic bislactones, named as cistobislactone A and cistobislactone B with unprecedented feature of henicos framework, based on extensive spectroscopic analyses. Cistobislactone B exhibited potential inhibition property against arachidonate 5-lipoxygenase (IC50 2.18 mM) than that demonstrated by cistobislactone A (IC50 2.54 mM) and standard non-steroidal anti-inflammatory agent ibuprofen (IC50 4.50 mM) thus signifying the higher anti-inflammatory activity of the cistobislactone B analogue. The studied macrocyclic bislactones exhibited promising antioxidant potential, in which cistobislactone B exhibited potential radical quenching (IC50 2.33 mM) and hydrogen peroxide scavenging (IC50 1.81 mM) activities that were proximal to the commercial anti-oxidant α-tocopherol (IC50 ~ 1.60 mM). This further reinforced its attenuation property against arachidonate 5-lipoxygenase. Considerably greater electronic properties coupled with balanced hydrophobicity of cistobislactone B could ascribe the superior ligand-receptor interfaces leading to its anti-inflammatory activity. Molecular docking analysis of cistobislactone B with 5-lipoxygenase recorded lesser docking score (−12.24 kcal mol−1) and binding energy (−11.24 kcal mol−1), which further supported its anti-inflammatory activity. Cistobislactone B, with six fold lesser value of inhibition constant (Ki 5.76 nM) towards 5-lipoxygenase than that displayed by cistobislactone A, could describe the superior protein-ligand interactions of the former. The undescribed cistobislactone B might be a potential natural anti-inflammatory lead to moderate the odds of inflammatory pathologies.