Algal Research-Biomass Biofuels and Bioproducts | 2019
Prospective natural anti-inflammatory drimanes attenuating pro-inflammatory 5-lipoxygenase from marine macroalga Gracilaria salicornia
Abstract
The 5-lipoxygenase-associated cascade has appeared as potential therapeutic target in attenuating inflammatory \npathologies. Progression and pathophysiology of inflammation have also shown potential involvement of oxidative \nstress and inflammatory pathways. Three drimane sesquiterpene quinols, characterised as 3-(hept-36- \nenyloxy)-decahydro-4,6a,12a,12b-tetramethyl-1H-benzo[a]xanthene-4,10,12-triol (1), 13-[[2-(hexyloxy)- \n2,5,5,8a-tetramethyldecahydro-1-naphthalenyl](methoxy)methyl]benzenol (2), and 1-butoxy-4,4,11b,11c-tetramethyl- \ndecahydrobenzo[kl]xanthen-10-ol (3) were purified from the organic extract of intertidal marine \nmacroalga Gracilaria salicornia, obtained from the southeast coastal regions of Indian peninsular. The 1H-benzo \n[a]xanthene-triol derivative (1) registered potential activities against pro-inflammatory 5-lipoxygenase (IC50 \n1.7 mM) and free radicals (IC50 1.3–1.6 mM). The in silico molecular modelling studies to designate 5-lipoxygenase \ninhibitory mechanism of the studied analogues and the comparison of docking parameters attributed \nthat the drimane sesquiterpene 1 exhibited least binding energy of −12.30 kcal mol−1, and showed effective \nhydrogen bonding interactions with the catalytic site of the enzyme. The higher electronic parameters and \npermissible hydrophobic-hydrophilic balance of the drimane sesquiterpene bearing 1H-benzo[a]xanthene-triol \nmoiety (1) appeared to constitute significant roles towards the attenuation of pro-inflammatory 5-lipoxygenase. \nPutative biosynthetic pathway of the studied compounds involving cyclisation of farnesyl diphosphate and \ncarbocationic rearrangement through a battery of enzyme-mediated cascade validated their structural attributions. \nThese results demonstrated that the drimane-type sesquiterpenoids with 1H-benzo[a]xanthene-triol framework \ncould be used as a potential therapeutic agent for the treatment of 5-lipoxygenase-mediated inflammatory \npathologies.