No abstract

No abstract

No abstract

Inflammations generate uneasiness. Multiple drug resistance imposes restrictions on the effectiveness of most existing drugs which necessitates either novel drug design or systematic derivatization of existing ones. This study adopts quantum mechanical and molecular docking approach to model and explore twenty derivatives of ibuprofen as potential non-steroidal antiinflammatory drug candidates in order to improve and update existing NSAIDs database, and alleviate global multiple drug resistance challenge taking ibuprofen as the standard. Optimization and calculation of the drug-like quantum chemical parameters of the compounds were conducted at DFT/B3LYP/6-31G* level of theory. Binding affinity, interaction and inhibition of the potential drug-candidates with human cyclooxygenase (COX-2) receptor were investigated using molecular docking studies. Pharmacokinetic properties were studied. The drug candidates interact effectively and spontaneously with the COX-2 receptor via hydrogen bonding and π-π stacking with greater binding affinity than ibuprofen except compounds 5 and 18. The energy gap, global hardness and softness, and chemical potential of the derivatives suggest that they are kinetically unstable, more chemically reactive than the parent drug and are effective electron donors. The docking studies show that compound 7 (3-(4-(3,3,3-trifluoro-2-methylpropyl)phenyl)butan-2-one) displays remarkably high binding affinity to the amino acid residues, ASN382 and HIS207, via H-bonding and π-π stacking interactions, respectively. From the pharmacokinetic studies, all the derivatives are not substrates to permeability glycoprotein (suggesting reduced therapeutic failure), not efficiently permeable to skin, can be absorbed by human intestine and can cross the blood brain barrier. Some derivatives are potential CYP1A2, CYP2D6 and CYP3A4 inhibitors. All the ibuprofen derivatives exhibit comparable drug-likeness with standard.

No abstract

No abstract

No abstract

Background Corrosion is a threat to material strength and durability. Electron-rich organic inhibitor may offer good corrosion mitigation potentials. In this work, anti-corrosion potentials of nine derivatives of 1H-indene-1,3-dione have been investigated using density functional theory (DFT) approach and molecular dynamics (MD) simulation. Chemical reactivity descriptors like energies of lowest unoccupied molecular orbital (ELUMO), highest occupied molecular orbital (EHOMO), electron affinity (A), ionization potential (I), energy gap (ΔEgap), global hardness (η), global softness (σ), electronegativity (χ), electrophilicity (ω), number of transferred electrons (ΔN) and back-donation (ΔEback-donation) were computed at DFT/B3LYP/6-31G(d) theoretical level. The local reactive sites and the charge partitioning on the compounds were studied using Fukui indices and molecular electrostatic potential (MEP) surface analysis. The adsorption behavior and the binding energy of the inhibitors on Fe (110) surface in hydrochloric acid solution were investigated using MD simulation. Results The high chemical reactivity, kinetic instability and good corrosion inhibition potentials demonstrated by the inhibitors are rationalized based on their high EHOMO, A, σ, ΔN, ΔEback-donation, and low ΔEgap, ELUMO, I and η. A wide difference of approximately 2.4–3.2 eV between the electronegativities of iron and the 1H-inden-1,3-diones suggests good charge transfer tendency from the latter to the low-lying vacant d-orbitals of iron. The heteroatoms (O and N) and the aromatic moieties are the nucleophilic sites on the inhibitors for effective adsorption on the metal surface as shown by condensed Fukui dual functions and MEP analysis. The MD simulation shows good interaction and strong binding energy between the inhibitor and Fe (110) surface. Conclusions Effective surface coverage and displacement of H3O+, Cl− and water molecules from Fe (110) surface by the inhibitors indicate good corrosion inhibition properties of the inden-1,3-diones. 2-((4,7-dimethylnaphthalen-1-yl)methylene)-1H-indene-1,3(2H)-dione display low energy gap, strongest binding interaction and most stabilized iron-inhibitor configuration, hence, the best anti-corrosion potential. Graphical abstract