期刊
ALGAL RESEARCH-BIOMASS BIOFUELS AND BIOPRODUCTS
卷 40, 期 -, 页码 -出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.algal.2019.101472
关键词
Gracilaria salicomia; Marine macroalga; Drimane sesquiterpene quinols; Pro-inflammatory 5-lipoxygenase; In silico molecular modelling; Biosynthetic pathway
资金
- Science and Engineering Research Board (SERB) Scheme from Department of Science and Technology, New Delhi, India [SR/S1/OC-96A/2012]
- Indian Council of Agricultural ResearchCentral Marine Fisheries Research Institute (ICAR-CMFRI)
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-3(6)-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-4,4,11 b,11 c- tetramethyl-decahydro benzo [k]lxanthen-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 lalxanthene-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 lalxanthene-triol framework could be used as a potential therapeutic agent for the treatment of 5-lipoxygenase-mediated inflammatory pathologies.
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