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Xenicanes attenuate pro-inflammatory 5-lipoxygenase: Prospective natural anti-inflammatory leads from intertidal brown seaweed Padina tetrastromatica

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Abstract

Two previously unreported xenicane class of novaxenicin-type xenicin diterpenoids (1–2) bearing cyclonona[d]furo [2,3-b]pyrandiol and three xeniolide-type diterpenoids with unprecedented octahydrocyclonona[c]pyran-3(1H)-one backbones (3–5) were separated from the organic extract of the intertidal seaweed Padina tetrastomatica (family Dictyotaceae), collected from southern India. The compounds were deduced to bear a xenicane moiety with a 2-oxabicyclo[7.4.0]tridecane cyclic system. The structures of these specialized metabolites were attributed based on the extensive nuclear magnetic resonance spectral analyses, and comparison of related compounds. Xeniolide-type diterpenes (3–5) registered significantly greater attenuation potential against pro-inflammatory 5-lipoxygenase (IC50 ~ 2.04 mM) than that exhibited by non-steroidal anti-inflammatory drug ibuprofen (IC50 4.50 mM, P< 0.05). The xeniolide derivative octahydro-1,7-dihydroxy-4-(41-hydroxy-42-methylpropyl)-6-(61-hydroxy-62-propenyl)-10-methyl-cyclonona[c]pyran-3(1H)-one (5) exhibited comparable antioxidant activity (DPPH IC50 1.73 mM) along with standard antioxidative agent α-tocopherol (IC50 < 2 mM). In silico molecular modelling studies were performed to designate the 5-lipoxygenase inhibitory mechanism of the xenicanes, and the comparison of docking parameters suggested that the xeniolide derivative 5 exhibited least binding energy of −11.56 kcal mol−1, and that was corroborated with its greater inhibition potential against the pro-inflammatory enzyme. These results demonstrated that the xeniolide-type diterpenoids with previously unreported δ-lactone cyclononane framework might constitute promising anti-inflammatory leads with pro-inflammatory 5-lipoxygenase enzyme inhibitory activities.

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Acknowledgements

The present work was supported by Science and Engineering Research Board (SERB) (grant number SR/S1/OC-96A/2012) of Department of Science and Technology, New Delhi, India. The authors thank the Director, Indian Council of Agricultural Research-Central Marine Fisheries Research Institute (ICAR-CMFRI), and Head, Marine Biotechnology Division, ICAR-CMFRI for guidance and support.

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  1. These authors contributed equally: Tima Antony, Kajal Chakraborty

Authors and Affiliations

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

    Tima Antony & Kajal Chakraborty

  2. Department of Chemistry, Mangalore University, Mangalagangothri, 574199, Karnataka State, India

    Tima Antony

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  1. Tima Antony
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  2. Kajal Chakraborty
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Correspondence to Kajal Chakraborty.

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Antony, T., Chakraborty, K. Xenicanes attenuate pro-inflammatory 5-lipoxygenase: Prospective natural anti-inflammatory leads from intertidal brown seaweed Padina tetrastromatica. Med Chem Res 28, 591–607 (2019). https://doi.org/10.1007/s00044-019-02322-8

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