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The current study on the antioxidant activity of kojic acid and 3‐hydroxypyridine‐4‐one derivatives was performed by implementation of density functional theory calculations with the B3LYP hybrid functional and the 6‐311++G** basis set in Polarizable Continuum Model of solvation. Compounds under evaluation were previously synthesized by our research group. The DPPH scavenging effect and the IC50 values in mM concentrations were evaluated. Subsequently, various electronic and energetic descriptors such as HOMO and LUMO energy gaps, bonding dissociation enthalpy of an OH bond, ionization potential, electron affinity, hardness, softness, NBOs and spin density of radical and neutral species were used to study antioxidant properties of investigated compounds. The computations detected two compounds, HP3 and HP4, with significant antioxidant activity. Energetic descriptors indicated that the SPLET mechanism is preferred over the other antioxidation mechanism and computational results were in accordance with the experimental results.

Background and purpose: Radicals produced by Fenton and Haber-Weiss reactions play detrimental roles in our body. Some oxidized proteins as toxic configurations are identified in amyloid-β deposits. These deposits mostly occur in conditions, such as Alzheimer’s disease. Here, we report the synthesis, evaluation of the antioxidant activity, and implementation of density functional theory (DFT) calculations of some4- [(benzo[ d ]thiazol-2-ylimino) methyl]phenol derivatives. The aim of this study was to provide a comparative theoretical-experimental approach to explain the antioxidant activities of the compounds. Experimental approach: Compounds were synthesized by the reaction between para hydroxybenzaldehyde and aminobenzothiazole derivatives. The scavenging activity of the compounds was evaluated. Various electronic and energetic descriptors such as high occupied molecular orbital and low unoccupied molecular orbital energy gaps, bonding dissociation enthalpy of OH bond, ionization potential, electron affinity, hardness, softness, and spin density of the radical and neutral species were calculated. DFT calculations with B3LYP hybrid functional and 6-311++ G** basis set in the polarizable continuum model were utilized to obtain these descriptors. Findings/Results: Ascorbic acid showed the best DPPH scavenging activity. However, 4d and 4c showed promising antioxidant activity. The values of EHOMO for 4c and 4d were closer to zero, thus, they showed the best scavenging activities. The computational results were in accordance with the experimental ones. The energetic descriptors indicated that the sequential proton loss-electron transfer mechanism is preferred over other mechanisms. Conclusion and implication: Antioxidant activity of 4-[(Benzo[ d ]thiazol-2-ylimino) methyl]phenol derivatives confirmed by experimental and theoretical documents proves them as novel antioxidants against amyloid-β based disease.

Researchers have focused on inhibiting acetylcholinesterase for Alzheimer's disease treatment. In this study, some novel AChE inhibitors were synthesized using hydroxypyridin‐4‐one plus benzylpiperidine scaffolds which were evaluated using Ellman's method. Accordingly, ((1‐(4‐methoxyphenethyl)piperidin‐4‐yl)amino)methyl)‐5‐hydroxy‐1‐methylpyridin‐4(1H)‐one (VIId) showed weaker but promising AChE inhibition compared to donepezil (IC50=143.090 nM). The average RMSD values of VIId was found to be 2.25 indicated less structural changes in the active site residues. The phenyl group of the phenyl‐ethyl‐N‐piperidine moiety of VIId formed hydrophobic interactions with Trp285 and Tyr340. There was a π‐cation interaction between nitrogen atom of piperidine ring and Phe294. Another π‐cation interaction was found between type 2 amine of linker and Trp85. Piperidine ring interacted with Tyr336, Tyr123, and Phe337 through hydrophobic interactions. Indeed, the VIId was predicted to be absorbed across the gastrointestinal tract, though it may be pumped out by P‐gp. Indeed, VIId can permeate through the blood brain barrier. MD simulation studies revealed that benzyloxy moiety plays a role similar to benzylpiperidine moiety of donepezil in binding to the active site residues. Also, carbonyl group functioned similar to indanone ketone group. Overall; further research on VIId may lead to introduction of a novel class of AChE inhibitors.