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.
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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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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.
Coronavirus outbreak is still a major public health concern. The high mutation ability of SARS-CoV-2 periodically delivers more transmissible and dangerous variants. Hence, the necessity for an ...efficient and inexpensive antiviral agent is urgent. In this work, pyrazolone-type compounds were synthesised, characterised using spectroscopic methods and theoretical tools, and evaluated in silico against proteins of SARS-CoV-2 responsible for host cell entry and reproduction processes, i.e. , spike protein (S), M pro , and PL pro . Five of twenty compounds are newly synthesised. In addition, the crystal structure of a pyrazolone derivative bearing a vanillin moiety is determined. The obtained in silico results indicate a more favourable binding affinity of pyrazolone analogues towards M pro , and PL pro in comparison to drugs lopinavir, remdesivir, chloroquine, and favipiravir, while in the case of S protein only lopinavir exerted higher binding affinity. Also, the investigations were performed on ACE2 and the spike RBD-ACE2 complex. The obtained results for these proteins suggest that selected compounds could express antiviral properties by blocking the binding to the host cell and viral spreading, also. Moreover, several derivatives expressed multitarget antiviral action, blocking both binding and reproduction processes. Additionally, in silico ADME/T calculations predicted favourable features of the synthesised compounds, i.e. , drug-likeness, oral bioavailability, as well as good pharmacokinetic parameters related to absorption, metabolism, and toxicity. The obtained results imply the great potential of synthesised pyrazolones as multitarget agents against SARS-CoV-2 and represent a valuable background for further in vitro investigations.
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Selected salicylidene imines were evaluated for their antioxidant and cytotoxic potentials. Several of them exerted potent scavenging capacity towards ABTS radical and hydrogen peroxide. The insight ...into the preferable antioxidative mechanism was reached employing density functional theory. In the absence of free radicals, the SPLET mechanism is dominant in polar surroundings, while HAT is prevailing in a non-polar environment. The results obtained for the reactions of the most active compounds with some medically relevant radicals pointed out competition between HAT and SPLET mechanisms. The assessment of their cytotoxic properties revealed inhibition of ER-a human breast adenocarcinoma cells or estrogen-independent prostate cancer cells. Molecular docking study with the cyclooxygenase (COX) 2 enzyme was performed to examine the most probable bioactive conformations and possible interactions between the tested derivatives and COX-2 binding pocket.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Pyrazolyl-phthalazine-dione derivatives (PPDs) were synthetized in the ionic liquid catalyzed one-pot multicomponent reaction of acetylacetone, 2,3-dihydrophthalazine-1,4-dione, and different ...aldehydes in moderate to good yields. Six new PPDs were obtained, and the crystal structure of 2-acetyl-1-(4-fluorophenyl)-3-methyl-1
-pyrazolo1,2-
phthalazine-5,10-dione (PPD-4) was determined. The most interesting structural features of the novel PPD-4 is the formation of a rather short intermolecular distance between the F atom of one molecule and the midpoint of the neighbouring six-membered heterocyclic ring. This interaction arranges all molecules into parallel supramolecular chains. UV-Vis spectra of all PPDs were acquired and compared to the simulated ones obtained with TD-DFT. All synthetized compounds were subjected to evaluation of their
antioxidative activity using a stable DPPH radical. It was shown that PPD-7, with a catechol motive, is the most active antioxidant, while PPD-9, with two neighbouring methoxy groups to the phenolic OH, exerted a somewhat lower, but significant antioxidative potential. The results of DFT thermodynamical study are in agreement with experimental findings that PPD-7 and PPD-9 should be considered as powerful radical scavengers. In addition, the obtained theoretical results (bond dissociation and proton abstraction energies) specify SPLET as a prevailing radical scavenging mechanism in polar solvents, and HAT in solvents with lower polarity. On the other hand, the obtained reaction enthalpies for inactivation of free radicals suggest competition between HAT and SPLET mechanisms, except in the case of the ˙OH radical in polar solvents, where HAT is labeled as prefered.
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N
-Salicylidene and
N
-vanillidene anil Schiff bases
SB
-
1
–
5
were evaluated for their iron-coordinating properties. For this purpose, reactions with Fe(III) chloride were performed. The obtained ...results showed that salicylaldehyde bases
SB-1
and
SB-2
are the best coordinating ligands among the investigated
SB
s. The corresponding complexes are obtained in good yield and investigated using UV–Vis spectrophotometry and IR spectroscopy. The inhibitory potential of
SB-1
–
5
against iron-containing enzyme lipoxygenase (LOX) was also tested. Salicylidene bases exerted better activity then vanilliden. The cytotoxic in vitro activities against human breast carcinoma MDA-MB-231 and human colon carcinoma HCT-116 cell lines were determined. Based on these results,
SB-1
and
SB-2
can be considered as interesting compounds for further in vivo investigations.
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Three-component Mannich reaction of acetophenone or 4-iodoacetophenone with a variety of substituted anilines and benzaldehyde, catalysed with diethanolammonium chloroacetate, was performed under ...mild conditions. Mannich bases (
), of which five are new, were obtained in good to excellent yields. All compounds were characterized using elemental analysis, NMR and IR. In addition, detailed experimental and simulated UV-Vis spectral characterization of these compounds is presented here for the first time.
antioxidative potential of synthetized
was evaluated using 2,2-diphenyl-1-picryl-hydrazyl radical and density functional theory (DFT) thermodynamical study. It was shown that compounds with anisidine moiety express moderate antioxidative activity. Mechanism of the organocatalysed Mannich reaction was thoroughly inspected by means of DFT. The reaction undergoes the hydrogen bonding-assisted mechanism. Moreover, the proposed rate determining step of the overall reaction is water elimination in the process of iminium ion formation. To the extent of our knowledge, this is the first detailed report on the influence of this type of catalyst on the formation of iminium ion, as a crucial intermediate for the whole reaction.
Over the years, pharmacological agents bearing antioxidant merits arose as beneficial in the prophylaxis and treatment of various health conditions. Hazardous effects of radical species ...hyperproduction disrupt normal cell functioning, thus increasing the possibility for the development of various oxidative stress‐associated disorders, such as cancer. Contributing to the efforts for efficient antioxidant drug discovery, a thorough in vitro and in silico assessment of antioxidant properties of 14 newly synthesized N‐pyrocatechoyl and N‐pyrogalloyl hydrazones (N‐PYRs) was accomplished. All compounds exhibited excellent antioxidant potency against the 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical. The extensive in silico analysis revealed multiple favorable features of N‐PYRs to inactivate harmful radical species, which supported the obtained in vitro results. Also, in silico experiments provided insights into the preferable antioxidant pathways. Prompted by these findings, the cytotoxicity effects and the influence on the redox status of cancer HCT‐116 cells and healthy fibroblasts MRC‐5 were evaluated. These investigations exposed four analogs exhibiting both cytotoxicity and selectivity toward cancer cells. Furthermore, the frequently uncovered antimicrobial potency of hydrazone‐type hybrids encouraged investigations on G+ and G– bacterial strains, which revealed the antibacterial potency of several N‐PYRs. These findings highlighted the N‐PYRs as excellent antioxidant agents endowed with cytotoxic and antibacterial features.
Novel N‐pyrocatechoyl and N‐pyrogalloyl phenolic hydrazones (N‐PYRs) were synthesized and assessed in antioxidant, cytotoxic, and antibacterial assays. The N‐PYRs exhibited excellent antioxidant potency against 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radicals. In silico calculations provided insights into potential antioxidant pathways. Also, N‐PYRs expressed cytotoxicity and selectivity toward HCT‐116 cancer cells, as well as antibacterial activity against diverse G+ and G– strains.
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