Polyether macrocyclic polyketide from the muricid gastropodChicoreus ramosusattenuates pro-inflammatory 5-lipoxygenase

Macrocyclic compounds of multifaceted structural scaffolds are being increasingly reported from the marine environment, and gaining commercial importance due to their ability to inhibit the pro-inflammatory mediators. An unreported polyether macrocyclic polyketide characterized as 6-(butoxy)-13,15,22-trihydroxy-3,18-dioxatricyclo[18.3.1.0(11,16)]tricosa-9,20-diene-4,8-dione was isolated from the marine gastropod molluscChicoreus ramosus(family Muricidae). The compound displayed potential anti-inflammatory property by inhibiting 5-lipoxygenase (IC(50)0.42 mg mL(-1)), which was analogous to the nonsteroidal anti-inflammatory agent aspirin (IC(50)0.38 mg mL(-1)) and superior to ibuprofen (IC(50)0.90 mg mL(-1)). Free radical scavenging abilities of the purified compound against oxidative agents (IC(50)0.22 mg mL(-1)) were comparable to the commercially available antioxidants (butylated hydroxyanisole, IC(50)0.25 mg mL(-1); butylated hydroxytoluene, IC(50)0.27 mg mL(-1)), and greater than alpha-tocopherol (IC(50)0.60 mg mL(-1)). Molecular docking studies of the studied polyketide analog against 5-lipoxygenase indicated that the docked ligand could potentially bind to the target site of the enzyme with a less binding energy (-9.33 kcal mol(-1)) and docking score (-10.23 kcal mol(-1)). The present study recognized the potential of macrocyclic polyketide possessing tricosa-9, 20-diene-4,8-dione framework isolated fromC. ramosusas a potential antioxidant and anti-inflammatory lead that could find its use in medicinal formulations.