Compounds from the plant world that possess antioxidant abilities are of special importance for the food and pharmaceutical industry. Coumarins are a large, widely distributed group of natural compounds, usually found in plants, often with good antioxidant capacity. The coumarin-hydroxybenzohydrazide derivatives were synthesized using a green, one-pot protocol. This procedure includes the use of an environmentally benign mixture (vinegar and ethanol) as a catalyst and solvent, as well as very easy isolation of the desired products. The obtained compounds were structurally characterized by IR and NMR spectroscopy. The purity of all compounds was determined by HPLC and by elemental microanalysis. In addition, these compounds were evaluated for their in vitro antioxidant activity. Mechanisms of antioxidative activity were theoretically investigated by the density functional theory approach and the calculated values of various thermodynamic parameters, such as bond dissociation enthalpy, proton affinity, frontier molecular orbitals, and ionization potential. In silico calculations indicated that hydrogen atom transfer and sequential proton loss–electron transfer reaction mechanisms are probable, in non-polar and polar solvents respectively. Additionally, it was found that the single-electron transfer followed by proton transfer was not an operative mechanism in either solvent. The conducted tests indicate the excellent antioxidant activity, as well as the low potential toxicity, of the investigated compounds, which makes them good candidates for potential use in food chemistry.

The recently declared global pandemic of a new human coronavirus called SARS-CoV-2, which causes respiratory tract disease COVID-19, has reached worldwide resonance and global efforts are being made to look for possible cures. Sophisticated molecular docking software, as well as available protein sequence and structure information, offer the ability to test the inhibition of two important targets of SARS-CoV-2, furin (FUR) enzyme, and spike glycoprotein, or spike protein (SP), that are key to host cell adhesion and hijacking. The potential inhibitory effect and mechanism of action of acid–base forms of different antiviral drugs, dominant at physiological pH, chloroquine (CQ), hydroxychloroquine (HCQ), and cinanserin (CIN), which have been shown to be effective in the treatment of SARS-CoV-2 virus, is reported with the special emphasis on their relative abundances. On the other hand, the potential inhibitory effect of the dominant acid–base forms of quercetin (Q) and its oxidative metabolite 2-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxy-3(2H) benzofuranone (BZF), which are constituents of traditional food products believed to exhibit antiviral effects, was also examined. The undertaken study includes the determination of the major energy contributions to the binding energy as well as in-depth analysis of amino acid residues at the active pocket and possible interactions. The approach that we propose here may be an additional strategy for combating the deadly virus by preventing the first step of the virus replication cycle. Preliminary research has shown that the investigated compounds exert an inhibitory effect against the SARS-CoV-2 furin enzyme and spiked glycoprotein through different acid–base forms. These investigations may be helpful in creating potential therapeutic agents in the fight against the SARS-CoV-2 virus. On the other hand, the results we predicted in this computational study may be the basis for new experimental in vitro and in vivo studies.

Coumarin derivatives are a class of compounds with pronounced biological activities that depend primarily on the present substituents. Four 3-methoxycarbonylcoumarin derivatives with substituents of different electron-donating/electron-withdrawing abilities (Br, NO₂, OH, and OMe) were investigated structurally by NMR, IR, and UV-VIS spectroscopies and density functional theory methods. The appropriate level of theory (B3LYP-D3BJ/6-311++G(d,p) was selected after comparing similar compounds’ experimental and theoretical structural parameters. The natural bond orbital and quantum theory of atoms in molecules were employed to investigate the intramolecular interactions governing stability. The electronic effects of substituents mostly affected the aromatic ring that the substituents are directly attached to. The antioxidant properties were investigated by electron paramagnetic resonance spectroscopy towards HO^•, and the percentages of reduction were between 13% (6-Br) and 23% (6-OMe). The protein binding properties towards transport proteins were assessed by spectrofluorimetry, molecular docking, and molecular dynamics (MD). The experimentally determined binding energies were well reproduced by molecular docking, showing that the spontaneity of ibuprofen binding was comparable to the investigated compounds. The flexibility of HSA in MD simulations depended on the substituents. These results proved the importance of electronic effects for the protein binding affinities and antioxidant properties of coumarin derivatives.

Ferulic acid (FA) is used in skin formulations for protection against the damaging actions of the reactive oxygen species (ROS) produced by UVA radiation. Possible underlying protective mechanisms are not fully elucidated. By considering the kinetics of proton-coupled electron transfer (PCET) and radical-radical coupling (RRC) mechanisms, it appears that direct scavenging could be operative, providing that a high local concentration of FA is present at the place of ^•OH generation. The resulting FA phenoxyl radical, after the scavenging of a second ^•OH and keto-enol tautomerization of the intermediate, produces 5-hydroxyferulic acid (5OHFA). Inhibition of the lipoxygenase (LOX) enzyme, one of the enzymes that catalyse free radical production, by FA and 5OHFA were analysed. Results of molecular docking calculations indicate favourable binding interactions of FA and 5OHFA with the LOX active site. The exergonicity of chelation reactions of the catalytic Fe²⁺ ion with FA and 5OHFA indicate the potency of these chelators to prevent the formation of ^•OH radicals via Fenton-like reactions. The inhibition of the prooxidant LOX enzyme could be more relevant mechanism of skin protection against UVA induced oxidative stress than iron chelation and assumed direct scavenging of ROS.

Two newly synthesized coumarin–palladium(II) complexes (C1 and C2) were characterized using elemental analysis, spectroscopy (IR and ¹H-¹³C NMR), and DFT methods at the B3LYP-D3BJ/6-311+G(d,p) level of theory. The in vitro and in silico cytotoxicity of coumarin ligands and their corresponding Pd(II) complexes was examined. For in vitro testing, five cell lines were selected, namely human cervical adenocarcinoma (HeLa), the melanoma cell line (FemX), epithelial lung carcinoma (A549), the somatic umbilical vein endothelial cell line (EA.hi926), and pancreatic ductal adenocarcinoma (Panc-1). In order to examine the in silico inhibitory potential and estimate inhibitory constants and binding energies, molecular docking studies were performed. The inhibitory activity of C1 and C2 was investigated towards epidermal growth factor receptor (EGFR), receptor tyrosine kinase (RTK), and B-cell lymphoma 2 (BCL-2). According to the results obtained from the molecular docking simulations, the inhibitory activity of the investigated complexes towards all the investigated proteins is equivalent or superior in comparison with current therapeutical options. Moreover, because of the low binding energies and the high correlation rate with experimentally obtained results, it was shown that, out of the three, the inhibition of RTK is the most probable mechanism of the cytotoxic activity of the investigated compounds.