In silico design of enzyme α-amylase and α-glucosidase inhibitors using molecular docking, molecular dynamic, conceptual DFT investigation and pharmacophore modelling.

Type 2 diabetes mellitus (T2DM) is characterized by elevated blood glucose levels and can lead to serious complications such as nephropathy, neuropathy, retinopathy and cardiovascular disease. The aim of this work is to identify and investigate the inhibition mechanism of natural flavonoids and phenolics acids against, the α-amylase (αA) and α-glucosidase (αG). Therefore, we used different approaches; such as conceptual DFT and pharmacophore mapping in addition to molecular mechanics, dynamics and docking simulations. Whereas, a close agreement was found out to decide that Linarin (Flavones) provides more optimized inhibition of αA and αG enzymes. Our results have shown that Linarin could be useful as preventative agent, and possibly therapeutic modality for the treatment of metabolic diseases.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.

Statistical analysis/theoretical investigations of novel vascular endothelial growth factor of Davanoide from Scolymus grandifloras Desf as potent anti-angiogenic drug properties.

Many pro-angiogenic factors acting directly or indirectly on the proliferation and differentiation of endothelial cells have been highlighted, in particular: VEGF ('Vascular Endothelial Growth Factor'), FGF ('Fibroblast Growth Factor'), PDGF ('Platelet-Derived Growth Factor'), VEGF exerts its pro-angiogenic activity by binding to the surface of receptors with tyrosine kinase activity (VEGFR). The first objective of this study was to elucidate the composition of the essential oil of the roots of Scolymus grandifloras Desf. The second aim was to describe the intra-species variation in essential oil composition in natural populations of 21 oil samples from different Algerian locations using statistical analysis and bioinformatical study of VEGFR inhibition. The essential oil isolated from the root parts, was a really source of Davanoide compounds. The results of the docking simulation revealed that davanone (Ligand 13) has an affinity to interact with cDNA, VEGF and its receptors. The ADMET properties and BOILED-Egg plot validate the compound 13 pass the brain barrier and have high absorption in the intestines with good bioavailability. The findings of this study contribute to the pharmacological knowledge and the therapeutic efficacy of davanone and can initiate the development of new anti-angiogenic drugs. Results showed that essential oil of Scolymus grandiflorus presented a large level of percentage of davanone, davanol D1 and 2-hydroxy davanone. These components may be a new source of nontoxic anticancer agents. However, an additional in vitro and/or in vivo experimental study should make it possible to verify the theoretical results obtained in silico.Communicated by Ramaswamy H. Sarma.