Free radicals often interact with vital proteins, violating their structure and inhibiting their activity. In previous studies, synthesis, characterisation, and the antioxidative properties of the ...five different coumarin derivatives have been investigated. In the tests of potential toxicity, all compounds exhibited low toxicity with significant antioxidative potential at the same time. In this paper, the radical scavenging activity of the abovementioned coumarin derivatives towards ten different radical species was investigated. It was found that all investigated compounds show good radical scavenging ability, with results that are in correlation with the results published in the previous study. Three additional mechanisms of radical scavenging activity were investigated. It was found that all three mechanisms are thermodynamically plausible and in competition. Interestingly, it was found that products of the Double Hydrogen Atom Transfer (DHAT) mechanism, a biradical species in triplet spin state, are in some cases more stable than singlet spin state analogues. This unexpected trend can be explained by spin delocalisation over the hydrazide bridge and phenolic part of the molecule with a low probability of spin pairing. Besides radical-scavenging activity, the pharmacokinetic and drug-likeness of the coumarin hybrids were investigated. It was found that they exhibit good membrane and skin permeability and potential interactions with P-450 enzymes. Furthermore, it was found that investigated compounds satisfy all criteria of the drug-likeness tests, suggesting they possess a good preference for being used as potential drugs.
Pharmaceutical and industrial utilization of synthetic chemicals has an immerse impact on the environment. In that sense, novel chemicals with potential for industrial application should be ...investigated for their behaviour in reactions with hydroxyl radical, simulating AOPs (Advanced Oxidation Processes). AOPs are known for being highly effective in wastewater management and natural water remediation. In this paper, exhaustive research on the radical scavenging activity of a newly synthesized coumarin derivative (4HCBH), as a representative of the series of coumarin-benzohydrazides with high antioxidative potential was conducted. This study took into consideration the pH value range significant for practically all living organisms (pH = 7.0–8.5). According to the experimentally obtained results, the 4HCBH showed an increase in radical scavenging activity, following the slight increase in pH values, which suggested that the formation of anionic form of 4HCBH is responsible for its antiradical activity. Further investigations led to the postulation of a novel mechanistic approach called Sequential Proton Loss Electron Transfer – Radical-Radical Coupling (SPLET-RRC), in which, by a series of steps, a new, stable compound was formed. Furthermore, it was demonstrated that the product generated through SPLET-RRC showed lower toxicity than the parent molecule.
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•Obtaining less toxic product in the reaction of coumarin-benzohydrazide with ●OH•Investigation of reaction between ●OH and a coumarin-benzohydrazide in the alkaline pH•Combining natural compounds to enhance their antiradical activity•Postulation of the novel mechanistic pathway of antiradical activity (SPLET-RRC)
The antioxidative capacity and structure–activity relationships of ten Schiff bases were investigated experimentally and theoretically. All compounds contain the aniline moiety, while the aldehyde ...part is either salicylaldehyde or vanillin. The DPPH assay was used to test the potential antioxidative activity of these compounds, and DFT study was used to investigate their electronic structures and provide insight into their structure–activity relationships. The effect of the position of the hydroxy, as well other groups present, on the antioxidative activity was examined. The possible radical scavenging mechanism was determined in polar (water and methanol), and nonpolar (benzene) solvents. Based on the experimental and computational results, compounds 7 and 8 exhibit the highest radical scavenging properties.
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•The radical scavenging study of BOH towards HO• was investigated by the DFT method.•The SOMO showed that the PCET is dominant mechanism for H atom abstraction.•Six positions in BOH ...structure were active for radical adduct formation with HO•.•The kinetically preferred pathway for the anionic species is electron transfer.•Molecular docking confirmed inhibitory effectiveness of BO− to the GLOI receptor.
Baicalein (BOH) is an essential flavone molecule with proven significant scavenging activity towards various reactive species, although the actual mechanism has not been fully elucidated. Three common mechanisms: Hydrogen Atom Abstraction (HAA), Radical Adduct Formation (RAF), and Electron Transfer (EA), for the reaction between BOH and HO• have been investigated thermodynamically and kinetically in water and penthylethanoate. Based on the pKa values of BOH, the percentages of various acid-base species were estimated and subsequently incorporated into the described procedures. Changes in Gibbs free energy of HAA reactions demonstrated the spontaneity of hydrogen transfer from each OH group of BOH with reaction rates of 1.8 × 107 and 7.5 × 104 M−1 s−1. This process occurred through Proton Coupled-Electron Transfer (PCET) mechanism. Reactions involving RAF processes were operable in six places, with rate constants ranging from 4.8 × 104 to 3.0 × 108 M−1 s−1. Reaction rates calculated for electron transfer from anionic species (BO-) were the kinetically most favorable reaction pathway of the order of 109 M−1 s−1, which unequivocally shows that these reactions are diffusion controlled. These results shed new light on BOH chemistry and its possible medical use. The molecular docking analysis was performed to identify the inhibition potency of the baicalein-anion against Glyoxalase I (GLOI) receptor. This study demonstrated that molecular docking analysis is an important tool for evaluating the interactions of biologically significant compounds, particularly their many acid-base forms.
A series of benzamide-dioxoisoindoline derivatives 3 was obtained, starting from phthalic anhydride and different benzoyl hydrazides 2, by ultrasound irradiation in water as solvent and without any ...catalyst. Five obtained compounds have been reported in this study for the first time and crystal structure of compound 3h was determined. All compounds were subjected to experimental determination of their antioxidative potential. DPPH test revealed that newly synthesized phenolic compounds 3d, 3e, and 3j are the best antioxidants. Additionally, probable radical scavenging pathway was analysed for reactions of the most active compounds and some radicals that can be found in living cells.
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•N-(1,3-dioxoisoindolin-2-yl)benzamide derivatives were obtained.•“On water” ultrasonic assisted methodology is presented.•Used method presents green approach according to green chemistry parameters.•Five compounds have been reported in this study for the first time.•All obtained compounds were tested for their in vitro antioxidative activity.
Cancer is still a relentless public health issue. Particularly, colorectal cancer is the third most prevalent cancer in men and the second in women. Moreover, cancer development and growth are ...associated with various cell disorders, such as oxidative stress and inflammation. The quest for efficient therapeutics is a challenging task, especially when it comes to achieving both cytotoxicity and selectivity. Herein, five series of phenolic
-acylhydrazones were synthesized and evaluated for their antioxidant potency, as well as their influence on HCT-116 and MRC-5 cells viability. Among 40 examined analogues, 20 of them expressed antioxidant activity against the DPPH radical. Furthermore, density functional theory was employed to estimate the antioxidant potency of the selected analogues from the thermodynamical aspect, as well as the preferable free-radical scavenging pathway. Cytotoxicity assay exposed enhanced selectivity of a number of analogues toward cancer cells. The structure-activity analysis revealed the impact of the type and position of the functional groups on both cell viability and selectivity toward cancer cells.
The phenolic compounds, which are rich in red wine, have gained considerable attention due to their antioxidant potential. Selected Serbian wines were analyzed for their antioxidant activity by DPPH ...test and the total content of phenolic compounds was determined by employing the Folin–Ciocalteu colorimetric method. The major polyphenols were determined by HPLC. The antioxidant activity was correlated with the amount of specific polyphenols (gallic acid, caffeic acid, catechin, epicatechin, myricetin, and kaempferol) by quantitative structure–activity relationship. The origin of the antioxidant potential of wines was discussed based on the individual activity of identified polyphenols and theoretical calculations (at APFD/6-311++G(d,p) level of theory). The thermodynamic parameters of free radical scavenging activity and reactivity towards DPPH
·
, HO
·
, and HOO
·
were explained with special emphasis on the effect of structure and intramolecular interactions in polyphenols. Based on the presented data, the positive effects of selected Serbian wines on humane health and biologically relevant free radicals are concluded.
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Two newly synthesized coumarin-palladium(II) complexes (C1 and C2) were characterized using elemental analysis, spectroscopy (IR and
H-
C 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.
The pyrazolone class comprises a variety of hybrid compounds displaying diverse biological actions. Although studied for decades, these compounds are still of interest due to their facile chemical ...transformations. In our previous work, we presented the synthetic route of functionalised pyrazolone derivatives. The presence of pyrazolone structural motif in many drugs, such as edaravone, prompted us to investigate the antioxidant features of the selected compounds. In this paper, we provide an extensive
and
description of the antioxidant properties of selected pyrazolone analogues. The obtained
results revealed their great antiradical potency against the DPPH radical (IC
values in the 2.6-7.8 μM range), where the best results were obtained for analogues bearing a catechol moiety. Density functional theory (DFT) was used to assess their antioxidant capacity from the thermodynamic aspect. Here, good agreement with
results was achieved. DFT was employed for the prediction of the most preferable radical scavenging pathway, also. In polar solvents, the SPLET mechanism is a favourable scavenging route, whereas in nonpolar solvents the HAT is slightly predominant. Furthermore, antioxidant mechanisms were studied in the presence of relevant reactive oxygen species. The obtained values of the reaction enthalpies with the selected radicals revealed that HAT is slightly prevailing in polar solvents, while the SPLET mechanism is dominant in nonpolar solvents. Regarding the well-known antioxidant features of the drug edaravone, these findings represent valuable data for this pyrazolone class and could be used as the basis for further investigations.
In this study, green synthesis of two derivatives of coumarin-hydroxybenzohydrazide, (
)-2,4-dioxo-3-(1-(2-(2,3,4-trihydroxybenzoyl)hydrazyl)ethylidene)-chroman-7-yl acetate (
), and (
...)-2,4-dioxo-3-(1-(2-(3,4,5-trihydroxybenzoyl)hydrazyl)ethylidene)chroman-7-yl acetate (
) is reported. Using vinegar and ethanol as a catalyst and solvent, the reactions were carried out between 3-acetyl-4-hydroxy-coumarin acetate and corresponding trihydroxybenzoyl hydrazide. The antioxidant potential of these compounds was investigated using the DPPH and ABTS assays, as well as the FRAP test. The obtained results reveal that even at very low concentrations, these compounds show excellent radical scavenging potential. The IC
values for C-HB
and C-HB
in relation to the DPPH radical are 6.4 and 2.5 μM, respectively, while they are 4.5 and 2.0 μM in relation to the ABTS radical. These compounds have antioxidant activity that is comparable to well-known antioxidants such as gallic acid, NDGA, and trolox. These results are in good correlation with theoretical parameters describing these reactions. Moreover, it was found that inhibition of DPPH
follows HAT, while inactivation of ABTS
follows SET-PT and HAT mechanisms. Additionally, coumarin-hydroxybenzohydrazide derivatives induced moderate cytotoxic activity and show significant potential to modulate redox status in HCT-116 colorectal cancer cells. The cytotoxicity was achieved via their prooxidative activity and ability to induce oxidative stress in cancer cells by increasing O
˙
concentrations, indicated by increased MDA and GSH levels. Thus, ROS manipulation can be a potential target for cancer therapies by coumarins, as cancer cells possess an altered redox balance in comparison to normal cells. According to the ADMET analysis, the compounds investigated show good pharmacokinetic and toxicological profiles similar to vitamin C and gallic acid, which makes them good candidates for application in various fields of industry and medicine.
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