A combined in vitro-in silico approach for the discovery of novel endogenous enzymatic and ctDNA sequence of bioactive molecules from aerial and root parts of Centaurea sulphurea as antioxidant's agents.

The excess free radicals not neutralized by the antioxidant defenses damage the essential macromolecules of our cells, causing abnormalities in the expression of genes and membrane receptors, cell proliferation or death, immune disorders, mutagenesis, deposits of proteins or lipofuschin in tissues. The first objective of this study was to elucidate the composition of the essential oil of the aerial and root part of Centaurea sulphurea during beginning of the vegetative cycle (March), beginning of the flowering stage (April) and full bloom (May/June) using GC/FID and GC/MS. The second aim was to describe the antioxidant activity using three methods (2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric-reducing antioxidant power (FRAP), ß-carotene bleaching assay) and bioinformatical study of ctDNA sequence and three endogenous enzymes inhibition. The essential oils obtained from the root during the full bloom period consisted mainly of caryophyllene oxide, aplotaxene and (Z)-phytol. While, the aerial parts were dominated by caryophyllene oxide, verridiflorol and humulene epoxide II. The results showed that essential oil presented an excellent antioxidant activity with IC50 values of 2.06 g/L and 1.29 g/L, for aerial and root parts, compared to butylated hydroxyltoluene (BHT) and Ethylenediaminetetraacetic acid (EDTA) controls and the nicotinamide adenine dinucleotide phosphate (NADPH) co-crystallized inhibitor. The results of the molecular docking revealed that (Z)-phytol (Ligand 39) has an affinity to interact with ctDNA sequence, and three targets Endogenous enzymes. The molecular dynamics study was conducted for the best inhibitors (Z)-phytol. A few key residues were identified at the binding site of receptors. The in-silico assessment of the ADME properties and BOILED-Egg plot reveals that compound (Z)-phytol (L39) is permeable to the blood brain barrier and have high lipophilicity and high coefficient of skin permeability in the intestines with good bioavailability. The ADMET analysis also showed that this oxygenated diterpene is safer to replace the synthetic drugs with side effects. Further testing is needed to assess its effectiveness in reducing oxidative stress for use in the pharmaceutical industry.Communicated by Ramaswamy H. Sarma.

Chemical composition/pharmacophore modelling- based, virtual screening, molecular docking and dynamic simulation studies for the discovery of novel superoxide dismutase (SODs) of bioactive molecules from aerial parts of Inula Montana as antioxydant's agents.

The accumulation of free radicals in the body develops chronic and degenerative diseases such as cancer, autoimmune diseases, rheumatoid arthritis, cardiovascular and neurodegenerative diseases. The first aim of this work was to study the chemical composition of Inula Montana essential oil using GC-FID and GC/MS analysis and the antioxidant activities using radical scavenging (DPPH) and the Ferric -Reducing Antioxidant Power (FRAP) tests. The second aim was to describe the assess the antioxidant activity and computational study of Superoxide Dismutase (SODs) and ctDNA inhibition. Sixty-nine compounds were identified in the essential oil of the aerial part of Inula montana. Shyobunol and α-Cadinol were the major compounds in the essential oil. The antioxidant power of the essential oil showed an important antioxidant effect compared to ascorbic acid and the methionine co-crystallized inhibitor. The results of the docking simulation revealed that E, E-Farnesyl acetate has an affinity to interact with binding models and the antioxidant activities of the ctDNA sequence and Superoxide Dismutase target. The penetration through the Blood-Brain Barrier came out to be best for E, E-Farnesyl acetate and E-Nerolidolacetate and was significantly higher than the control molecule and Lref. Finally, the application of ADMET filters gives us positive information on the compound E, E-Farnesyl acetate, which appears as a new inhibitor potentially more active towards ctDNA and SODs target. The active compounds, E,E-Farnesyl acetate can be used as templates for further development of more potent antioxidative agents.Communicated by Ramaswamy H. Sarma.