Prospective natural anti-inflammatory drimanes attenuating proinflammatory 5-lipoxygenase from marine macroalga Gracilaria salicornia
CMFRI Repository
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Relation |
http://eprints.cmfri.org.in/13642/
https://www.sciencedirect.com/science/article/pii/S221192641830866X?via%3Dihub https://doi.org/10.1016/j.algal.2019.101472 |
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Title |
Prospective natural anti-inflammatory drimanes attenuating proinflammatory 5-lipoxygenase from marine macroalga Gracilaria salicornia |
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Creator |
Chakraborty, Kajal
Antony, Tima Joy, Minju |
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Subject |
Bioactive compound
Biochemistry Algae |
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Description |
The 5-lipoxygenase-associated cascade has appeared as potential therapeutic target in attenuating inflammatory pathologies. Progression and pathophysiology of inflammation have also shown potential involvement of oxidative stress and inflammatory pathways. Three drimane sesquiterpene quinols, characterised as 3-(hept-36- enyloxy)-decahydro-4,6a,12a,12b-tetramethyl-1H-benzo[a]xanthene-4,10,12-triol (1), 13-[[2-(hexyloxy)- 2,5,5,8a-tetramethyldecahydro-1-naphthalenyl](methoxy)methyl]benzenol (2), and 1-butoxy-4,4,11b,11c-tetramethyl- decahydrobenzo[kl]xanthen-10-ol (3) were purified from the organic extract of intertidal marine macroalga Gracilaria salicornia, obtained from the southeast coastal regions of Indian peninsular. The 1H-benzo [a]xanthene-triol derivative (1) registered potential activities against pro-inflammatory 5-lipoxygenase (IC50 1.7 mM) and free radicals (IC50 1.3–1.6 mM). The in silico molecular modelling studies to designate 5-lipoxygenase inhibitory mechanism of the studied analogues and the comparison of docking parameters attributed that the drimane sesquiterpene 1 exhibited least binding energy of −12.30 kcal mol−1, and showed effective hydrogen bonding interactions with the catalytic site of the enzyme. The higher electronic parameters and permissible hydrophobic-hydrophilic balance of the drimane sesquiterpene bearing 1H-benzo[a]xanthene-triol moiety (1) appeared to constitute significant roles towards the attenuation of pro-inflammatory 5-lipoxygenase. Putative biosynthetic pathway of the studied compounds involving cyclisation of farnesyl diphosphate and carbocationic rearrangement through a battery of enzyme-mediated cascade validated their structural attributions. These results demonstrated that the drimane-type sesquiterpenoids with 1H-benzo[a]xanthene-triol framework could be used as a potential therapeutic agent for the treatment of 5-lipoxygenase-mediated inflammatory pathologies. |
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Date |
2019
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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/13642/1/Kajal%20Chakraborty_2019_Algal%20Research_Natural%20anti-inflammatory%20drimanes%20attenuating%20pro-inflammatory%205-lipoxygenase%20from%20marine%20macroalga%20Gracilaria%20salicornia.pdf
Chakraborty, Kajal and Antony, Tima and Joy, Minju (2019) Prospective natural anti-inflammatory drimanes attenuating proinflammatory 5-lipoxygenase from marine macroalga Gracilaria salicornia. Algal Research, 40. pp. 1-11. |
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