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Ellipyrones A-B, from oval bone cuttlefish Sepia elliptica: Antihyperglycemic γ-pyrone enclosed macrocyclic polyketides attenuate dipeptidyl peptidase-4 and carbolytic enzymes

Medicinal Chemistry Research volume 31, pages 462–473 (2022)Cite this article

Abstract

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 γ-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 α-glucosidase (IC50 0.74 mM) and α-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 γ-pyrone fused macrocyclic poyketides could be used as pharmaco-active food supplement against hyperglycemia-associated ailments.

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Fig. 1
Fig. 2

Data availability

The chromatographic and spectroscopic spectral data are included as supplementary information.

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Acknowledgements

The authors gratefully acknowledge the funding by the Indian Council of Agricultural Research (ICAR, New Delhi, India) under Central Marine Fisheries Research Institute (ICAR-CMFRI) project “Development of Bioactive Pharmacophores from Marine Organisms” (MBT/HLT/SUB23). The authors are grateful to the Director, ICAR-CMFRI, and Head, Marine Biotechnology Division of ICAR-CMFRI for facilitating the research activities. The authors are thankful to the Chairman, Department of Chemistry, Mangalore University (Karnataka, India) for providing with necessary support.

Author contributions

SKP and KC designed research, conducted experiments, and analyzed data. KC acquired funds and conceptualized the work. SKP drafted the manuscript. KC reviewed and edited the manuscript. All authors read and approved the manuscript.

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Author notes

  1. These authors contributed equally: Silpa Kunnappilly Paulose, Kajal Chakraborty

Authors and Affiliations

  1. Department of Chemistry, Mangalore University, Mangalagangothri, 574199, Mangalore, Karnataka, India

    Silpa Kunnappilly Paulose

  2. Marine Bioprospecting Section of Marine Biotechnology Division, Central Marine Fisheries Research Institute, Ernakulam North, P.B. No. 1603, Cochin, 682018, Kerala, India

    Kajal Chakraborty

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  1. Silpa Kunnappilly Paulose
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  2. Kajal Chakraborty
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Correspondence to Kajal Chakraborty.

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Paulose, S.K., Chakraborty, K. Ellipyrones A-B, from oval bone cuttlefish Sepia elliptica: Antihyperglycemic γ-pyrone enclosed macrocyclic polyketides attenuate dipeptidyl peptidase-4 and carbolytic enzymes. Med Chem Res 31, 462–473 (2022). https://doi.org/10.1007/s00044-022-02846-6

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Keywords

  • Sepia elliptica
  • Sepiidae
  • γ-pyrone enclosed macrocyclic polyketides
  • Ellipyrones A-B
  • Anti-hyperglycemic