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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.

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Acknowledgements

We are grateful to Indian Council of Agricultural Research (ICAR) funded Consortium Research Platform Project on “Health Food” (grant number ICAR/HF/2012-2017). We thank the Director, Central Marine Fisheries Research Institute for guidance and support. Thanks are due to the Head, Marine Biotechnology Division, Central Marine Fisheries Research Institute to facilitate the research activity.

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Correspondence to Kajal Chakraborty.

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Salas, S., Chakraborty, K. Polyether macrocyclic polyketide from the muricid gastropod Chicoreus ramosus attenuates pro-inflammatory 5-lipoxygenase. Med Chem Res 29, 1976–1985 (2020). https://doi.org/10.1007/s00044-020-02614-4

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Keywords

  • Gastropod mollusc
  • Chicoreus ramosus
  • Polyether macrocyclic polyketide
  • Antioxidant
  • Anti-inflammatory
  • Pro-inflammatory 5-lipoxygenase