Anti-inflammatory polyether triterpenoids from the marine macroalga Gracilaria salicornia: Newly described natural leads attenuate proinflammatory 5-lipoxygenase and cyclooxygenase-2
CMFRI Repository
View Archive InfoField | Value | |
Relation |
http://eprints.cmfri.org.in/14106/
https://www.sciencedirect.com/science/article/pii/S2211926419306599?via%3Dihub https://doi.org/10.1016/j.algal.2020.101791 |
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Title |
Anti-inflammatory polyether triterpenoids from the marine macroalga Gracilaria salicornia: Newly described natural leads attenuate proinflammatory 5-lipoxygenase and cyclooxygenase-2 |
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Creator |
Antony, Tima
Chakraborty, Kajal |
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Subject |
Bioprospecting
Bioactive compounds Algae |
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Description |
5-Lipoxygenase (5-LOX)/cyclooxygenase-2 (COX-2) were found to be the two major inducible pro-inflammatory enzymes catalysing the rate-limiting stage in the development of pro-inflammatory prostaglandins/thromboxanes by COX-2 pathway and leukotrienes by 5-LOX pathway. Instantaneous quenching of COX-2/5-LOX-associated cascade is an important therapeutic objective in the attenuation of inflammatory pathologies. Two polyether triterpenoids, characterised as 15-(octahydro-7-(4,5-dihydro-3-methoxy-2,6-dimethyl-2H-pyran-6-yl)-10-methylpyrano[3,2-b]pyran-14-yl)-18-(19-methyl-23-methyleneoxepan-19-yl)pent-15-en-18-ol (1) and tetrahydro-6-(hexahydro-13-((tetrahydro-18-(23-hydroxy-23-methylheptan-19-yl)-15-methylfuran-15-yl)methyl)-10-methyl-2H-furo[3,2-b]pyran-7-yl)-2,2,6-trimethyl-2H-pyran-3-yl butyrate (2) were isolated from the organic extract of the marine macroalga, Gracilaria salicornia harvested from southeast-coastal zones of the Indian peninsular. Polyether analogue bearing trimethyl-2H-pyran-3-yl butyrate moiety (2) disclosed potent attenuation properties against 5-LOX (IC50 1.89 mM) and COX-2 (IC50 1.87 mM) enzymes. In-silico molecular docking methods designated the anti-inflammatory mechanisms of isolated compounds and their comparison of docking factors assigned that the polyether 2 displayed the smallest binding energy of −10.29 and −10.96 kcal mol−1 in COX-2 and 5-LOX active sites, respectively and designated competent hydrogen-bonding associations with the enzymatic catalytic regions. Greater electronic factors along with lesser steric bulk of the polyether 2 bearing furanyl-furo[3,2-b]pyran-2H-pyran moiety was found to have noteworthy functional roles to attenuate the inflammatory enzymes. Proposed bio-synthetic origin leading to the polyether analogues comprising the cyclization of squalene epoxides through the sequences of enzyme-catalysed cascade corroborated their structural attributions. These reports designated that polyether triterpenoid enclosing furanyl-furo[3,2-b]pyran-2H-pyran skeleton might be considered as a prospective anti-inflammatory therapeutic source to alleviate COX-2 and 5-LOX-mediated inflammatory pathologies.
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Date |
2020
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Type |
Article
PeerReviewed |
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Format |
text
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Language |
en
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Identifier |
http://eprints.cmfri.org.in/14106/1/Algal%20Research_2020_Kajal%20Chakraborty_Anti-inflammatory%20polyether%20triterpenoids%20from%20the%20marine%20macroalga%20Gracilaria%20salicornia.pdf
Antony, Tima and Chakraborty, Kajal (2020) Anti-inflammatory polyether triterpenoids from the marine macroalga Gracilaria salicornia: Newly described natural leads attenuate proinflammatory 5-lipoxygenase and cyclooxygenase-2. Algal Research, 47. pp. 1-15. |
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