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Anti-inflammatory scalarane-type sesterterpenes, erectascalaranes A–B, from the marine sponge Hyrtios erectus attenuate pro-inflammatory cyclooxygenase-2 and 5-lipoxygenase

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Abstract

Chemical investigation of demosponge Hyrtios erectus (family Thorectidae) resulted in the identification of two scalarane-type sesterterpenes, erectascalaranes A–B, which were characterized as 3-((but-35-enyloxy)methyl)-icosahydro-11-hydroxy-4,4,8,10,13-pentamethyl-20-oxochryseno[2,1-c]furan-12-yl acetate (erectascalarane A) and 3-((but-35-enyloxy)methyl)-hexadecahydro-11-hydroxy-4,4,8,10,13-pentamethylchryseno[2,1-c]furan-20(5bH)-one (erectascalarane B) using detailed spectroscopic experiments. Erectascalarane A exhibited significantly greater attenuation property against pro-inflammatory cyclooxygenase-2 (IC50 0.80 mM) than that displayed by erectascalarane B (IC50 ~ 1 mM). Erectascalarane A was found to be a potential inhibitor against 5-lipoxygenase (IC50 1.21 mM), and its activity was significantly higher than that displayed by standard anti-inflammatory agent ibuprofen (IC50 4.50 mM, p < 0.05). Greater anti-inflammatory selectivity index of erectascalarane A (1.15) than ibuprofen (0.43) also accounted for greater selectivity of the former against cyclooxygenase-2. Erectascalarane A also exhibited significantly greater antioxidant activities against oxidants (IC50 ~ 0.8 mM) than the standard α-tocopherol (IC50 > 1.5 mM). Lesser docking parameters obtained for erectascalarane A at the active site of COX-2 and greater electronic factors acquired from structure–activity analyses (topological polar surface area 82.06) were also in agreement with greater anti-inflammatory activity. Lesser steric bulk and greater electronic properties combined with lower binding energy with cyclooxygenase-2 further reinforced the significant anti-inflammatory potential of erectascalarane A.

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Acknowledgements

This work was funded by the Indian Council of Agricultural Research-Central Marine Fisheries Research Institute (ICAR-CMFRI), India, under the project titled as “Development of Bioactive Pharmacophores from Marine Organisms” (grant number MBT/HLT/SUB23). The authors thank the Director, ICAR-CMFRI, and Head, Marine Biotechnology Division, ICAR-CMFRI, for guidance and support.

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  1. These authors contributed equally: Prima Francis, Kajal Chakraborty

Authors and Affiliations

  1. Central Marine Fisheries Research Institute, Ernakulam North, P.B. No. 1603, Cochin, 682018, India

    Prima Francis & Kajal Chakraborty

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

    Prima Francis

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  1. Prima Francis
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  2. Kajal Chakraborty
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Correspondence to Kajal Chakraborty.

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Francis, P., Chakraborty, K. Anti-inflammatory scalarane-type sesterterpenes, erectascalaranes A–B, from the marine sponge Hyrtios erectus attenuate pro-inflammatory cyclooxygenase-2 and 5-lipoxygenase. Med Chem Res 30, 886–896 (2021). https://doi.org/10.1007/s00044-020-02682-6

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