First report of chromenyl derivatives from spineless marine cuttlefish Sepiella inermis: Prospective antihyperglycemic agents attenuate serine protease dipeptidyl peptidase-IV.

Abstract

Spineless marine cuttlefish Sepiella inermis has been considered as a popular dietary cephalopod species in Asian and Mediterranean coasts. Bioassay-directed purification of organic extract of S. inermis ensued in the characterization of two chromenyl derivatives. The studied compounds exhibited significantly greater antioxidant potencies (IC50 ≤0.5mg/ml) when compared with α-tocopherol. The substituted 1H-isochromenyloxy-11-hydroxyethyl pentanoate isoform (compound 1) efficiently inhibited the carbolytic enzymes along with key regulator of insulin secretion dipeptidyl peptidase-IV (IC50 0.16mg/ml). The molecular docking simulations displayed optimum binding affinity of the compound 1 (-10.01kcal/mol) with dipeptidyl peptidase-IV and lesser inhibition constant (Ki 46.41nM), which along with its permissible hydrophobic-hydrophilic balance (log Pow ~2) appeared to play significant roles in its greater antihyperglycemic activity compared to other studied chromenyl isoform. The greater antioxidant and antidiabetic properties of compound 1 could be utilized as an important natural lead against hyperglycemic-related disorders. PRACTICAL APPLICATIONS: The edible spineless marine cuttlefish Sepiella inermis are ubiquitously available in Asian and Mediterranean coasts. The sequential chromatographic purification of the organic extract of S. inermis led to the identification of two pure chromenyl chemotypes. The metabolites with substituted 1H-isochromenyloxy-11-hydroxyethyl pentanoate isoform (compound 1) displayed potential antioxidative and antihyperglycemic activities compared to the chemotype (2) bearing 3H-isochromen-5-yl moiety. The attenuating potential of chromenyl chemotype 1 against carbohydrate hydrolyzing enzymes and insulin secretion regulator attributed towards its efficiency as an important natural lead against postprandial hyperglycemia and incretin hormone regulation to maintain glucose homeostasis in the biological system. The chromenyl metabolites isolated from S. inermis could be utilized as a functional food ingredient in the nutraceutical formulations against hyperglycemic-related disorders.