Marine cuttlefish derived 2H-benzochromenone: Pharachromenone as a dual inhibitor of pro-inflammatory 5-lipoxygenase and cyclooxygenase-2.

Abstract

Cephalopod cuttlefish, Sepia pharaonis, has been considered as a commercially important resource, which is widely regarded as nutritious food in the southwest of Indian and Mediterranean coasts. Chemical analysis of the crude extract of S. pharaonis resulted in the isolation of an undescribed 2H-benzochromenone, pharachromenone, which was characterized as methyl-2″-(7-hydroxy-4-(5'-methylpent-5'-en-1'-yl-oxy-methyl)-2-oxo-2H-benzo[h]chromen-5-yl-methyl)-butanoate by mass and nuclear magnetic resonance spectral experiments. Pharachromenone revealed effective biopotency against 5-lipoxygenase (IC50 1.85mM) and cyclooxygenase-2 (IC50 0.52mM) than that displayed by nonsteroidal anti-inflammatory drug ibuprofen (IC50 4.36mM, p<.05). Promising antioxidant property for pharachromenone (IC50 1.42-1.61mM) compared with those exhibited by antioxidative agents butylated hydroxyl anisole (BHA) and α-tocopherol (IC50 1.40-1.90mM) could conceivably validate its dual inhibition potential against 5-lipoxygenase and cyclooxygenase-2. Greater electronic parameters, lesser steric bulkiness, along with acceptable lipophilic-hydrophobic balance significantly contributed toward its promising anti-inflammatory activities. Molecular docking studies showing significantly greater inhibition constant (Ki) 8.24nM and binding energy (-11.03kcal/mol) of pharachromenone than the standard ibuprofen (Ki 4.65μM, binding energy -7.27kcal/mol) at the binding site of 5-lipoxygenase recognized its noncompetitive binding, which could describe the promising anti-inflammatory potential. Pharachromenone could be developed as a functional food component against oxidative stress-related inflammatory disorders. PRACTICAL APPLICATIONS: The cuttlefish Sepia pharaonis (family Sepiidae) comprises a major share in the global fishery sector due to its culinary delicacy and nutritionally valued high-quality meat. Furthermore, cephalopod mollusks are gaining pharmaceutical acceptance as resources to derive bioactive compounds with therapeutic significance. Bioassay-guided chromatographic fractionation of crude extract of S. pharaonis could result in the isolation of a 2H-benzochromenone derivative, pharachromenone exhibiting potent antioxidant and anti-inflammatory properties. This study recognized the therapeutic potential of a marine cuttlefish-originated food constituent against inflammatory conditions, and could be anticipated as a high-value functional food lead to minimize oxidative stress-related inflammatory disorders.