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Stomopneulactone D from long-spined sea urchin Stomopneustes variolaris: Anti-inflammatory macrocylic lactone attenuates cyclooxygenase-2 expression in lipopolysaccharide-activated macrophages

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Relation http://eprints.cmfri.org.in/14424/
https://www.sciencedirect.com/science/article/pii/S0045206820314371?via%3Dihub
https://doi.org/10.1016/j.bioorg.2020.104140
 
Title Stomopneulactone D from long-spined sea urchin Stomopneustes variolaris:
Anti-inflammatory macrocylic lactone attenuates cyclooxygenase-2
expression in lipopolysaccharide-activated macrophages
 
Creator Chakraborty, Kajal
Francis, Prima
 
Subject Bioactive compounds
Echinoderms
Sea Urchin
 
Description Cyclooxygenase-2 is one of the prominent enzymes to cause an increased production of prostaglandins during
inflammation and immune responses. Cyclooxygenase-2 expression is up-regulated in inflammatory conditions
owing to the induction by different inflammatory stimuli including cytokines, and therefore, the expression
studies of cyclooxygenase-2 in lipopolysaccharide-induced macrophage cells (RAW 264.7 cell line) could be used
for screening of the compounds with anti-inflammatory potential. The present study evaluated the anti-inflammatory
properties of four homologous stomopneulactones A-D, classified under the class of macrocyclic
lactones isolated from the solvent extract of the long-spined sea urchin Stomopneustes variolaris
(family Stomopneustidae) in the lipopolysaccharide-induced macrophages. The structures of these isolated
compounds were assigned using detailed spectroscopic techniques. Stomopneulactone D bearing 5-butyl-4-hydroxy-
12-oxo-1-oxa-5,9-cyclododecadienyl moiety exhibited relatively greater anti-inflammatory potentials
against cyclooxygenase-2 (IC50 ~ 2 mM) and 5-lipoxygenase (IC50 2.6 mM) than those displayed by other
macrocyclic lactones. The studied compounds displayed higher selectivity index values (anti-cyclooxygenase-
1IC50/anti-cyclooxygenase-2IC50 > 1), which designated the selective anti-inflammatory potentials of the
macrocyclic lactones against inducible inflammatory mediators than those exhibited by the anti-inflammatory
agent ibuprofen (0.43). The in silico molecular modelling analyses of the stomopneulactones with cyclooxygenase-
2/5-lipoxygenase enzymes recorded lowest binding energy (−7.71 and −9.60 kcal mol−1, respectively)
and docking score (−8.82 and −11.12 kcal mol−1, respectively) for stomopneulactone D along with its
higher electronic parameter (topological polar surface area of 72.83), which further confirmed its greater antiinflammatory
potential than other compounds in the series. Stomopneulactone D also inhibited the generation of
inducible nitric oxide synthase, intracellular reactive oxygen species, along with 5-lipoxygenase and cyclooxygenase-
2 in the lipopolysaccharide-stimulated macrophage cells. Additionally, the studied macrocyclic lactone
decreased the mRNA expression of cyclooxygenase-2 in the inflammatory cells in dose-dependent manner, which
demonstrated the therapeutic potential of stomopneulactone D in down-regulating the inflammatory pathogenesis.
 
Date 2020
 
Type Article
PeerReviewed
 
Format text
 
Language en
 
Identifier http://eprints.cmfri.org.in/14424/1/Bioorganic%20Chemistry_2020_Kajal%20Chakraborty.pdf
Chakraborty, Kajal and Francis, Prima (2020) Stomopneulactone D from long-spined sea urchin Stomopneustes variolaris: Anti-inflammatory macrocylic lactone attenuates cyclooxygenase-2 expression in lipopolysaccharide-activated macrophages. Bioorganic Chemistry, 103. pp. 1-15.