Xenicanes attenuate pro-inflammatory 5-lipoxygenase: Prospective natural anti-inflammatory leads from intertidal brown seaweed Padina tetrastromatica
- Central Marine Fisheries Research Institute, Marine Bioprospecting Section of Marine Biotechnology Division (India)
Two previously unreported xenicane class of novaxenicin-type xenicin diterpenoids (1–2) bearing cyclonona[d]furo [2,3-b]pyrandiol and three xeniolide-type diterpenoids with unprecedented octahydrocyclonona[c]pyran-3(1H)-one backbones (3–5) were separated from the organic extract of the intertidal seaweed Padina tetrastomatica (family Dictyotaceae), collected from southern India. The compounds were deduced to bear a xenicane moiety with a 2-oxabicyclo[7.4.0]tridecane cyclic system. The structures of these specialized metabolites were attributed based on the extensive nuclear magnetic resonance spectral analyses, and comparison of related compounds. Xeniolide-type diterpenes (3–5) registered significantly greater attenuation potential against pro-inflammatory 5-lipoxygenase (IC{sub 50} ~ 2.04 mM) than that exhibited by non-steroidal anti-inflammatory drug ibuprofen (IC{sub 50} 4.50 mM, P< 0.05). The xeniolide derivative octahydro-1,7-dihydroxy-4-(4{sup 1}-hydroxy-4{sup 2}-methylpropyl)-6-(6{sup 1}-hydroxy-6{sup 2}-propenyl)-10-methyl-cyclonona[c]pyran-3(1H)-one (5) exhibited comparable antioxidant activity (DPPH IC{sub 50} 1.73 mM) along with standard antioxidative agent α-tocopherol (IC{sub 50} < 2 mM). In silico molecular modelling studies were performed to designate the 5-lipoxygenase inhibitory mechanism of the xenicanes, and the comparison of docking parameters suggested that the xeniolide derivative 5 exhibited least binding energy of −11.56 kcal mol{sup −1}, and that was corroborated with its greater inhibition potential against the pro-inflammatory enzyme. These results demonstrated that the xeniolide-type diterpenoids with previously unreported δ-lactone cyclononane framework might constitute promising anti-inflammatory leads with pro-inflammatory 5-lipoxygenase enzyme inhibitory activities.
- OSTI ID:
- 22936199
- Journal Information:
- Medicinal Chemistry Research (Print), Journal Name: Medicinal Chemistry Research (Print) Journal Issue: 4 Vol. 28; ISSN 1054-2523
- Country of Publication:
- United States
- Language:
- English
Similar Records
Transcriptomic Analysis of Arachidonic Acid Pathway Genes Provides Mechanistic Insight into Multi-Organ Inflammatory and Vascular Diseases
A novel synthetic derivative of melatonin, 5-hydroxy-2’-isobutyl-streptochlorin (HIS), inhibits inflammatory responses via regulation of TRIF-dependent signaling and inflammasome activation