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  • Ellipyrones A-B, from oval bone cuttlefish Sepia elliptica

    Dipeptidyl peptidase-4 is an integral membrane serine exopeptide catalyzing the deactivation of incretin hormones, which are important physiological substrates to release insulin from pancreatic beta cells and augmenting glucagon production, and thus, regulating postprandial hyperglycemia. Undescribed Y-pyrone enclosed macrocyclic poyketides ellipyrones A-B were purified from the crude solvent extract of marine cuttlefish, Sepia elliptica by repeated chromatographic fractionation. Ellipyrone A showed greater inhibition potential against dipeptidyl peptidase-4 (IC50 0.35 mM) than that demonstrated by ellipyrone B (IC50 0.48 mM), and was proportionate with those exhibited by reference dipeptidyl peptidase inhibitor diprotin A (IC50 0.29 mM). Ellipyrone A also recorded commensurate anti-carbolytic property against Y-glucosidase (IC50 0.74 mM) and Y-amylase (IC50 0.59 mM) when compared with anti-hyperglycemic agent acarbose. Greater structural descriptors of ellipyrone A (topological surface area of 116.2) in conjunction with permissible hydrophobic criterion (n-octanol-water partition ratio of 0.37) further attributed its prospective dipeptidyl peptidase attenuation property owing to the transcelluar mechanism involved in the antidiabetic drug action. These isolated Y-pyrone fused macrocyclic poyketides could be used as pharmaco-active food supplement against hyperglycemia-associated ailments.


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