Polyether macrocyclic polyketide from the muricid gastropod Chicoreus ramosus attenuates pro-inflammatory 5-lipoxygenase

Abstract

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[18.3.1.011,16]tricosa-9,20-diene-4,8-dione was isolated from the marine gastropod mollusc Chicoreus ramosus (family Muricidae). The compound displayed potential anti-inflammatory property by inhibiting 5-lipoxygenase (IC50 0.42 mg mL−1), which was analogous to the nonsteroidal anti-inflammatory agent aspirin (IC50 0.38 mg mL−1) and superior to ibuprofen (IC50 0.90 mg mL−1). Free radical scavenging abilities of the purified compound against oxidative agents (IC50 0.22 mg mL−1) were comparable to the commercially available antioxidants (butylated hydroxyanisole, IC50 0.25 mg mL−1; butylated hydroxytoluene, IC50 0.27 mg mL−1), and greater than α-tocopherol (IC50 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 from C. ramosus as a potential antioxidant and anti-inflammatory lead that could find its use in medicinal formulations.