Prediction, in silico antioxidant activity, and targeted synthesis of sterically hindered phenol azomethine derivatives
Molecular design and synthesis of a new series of biologically active azomethines containing a sterically hindered phenolic fragment were carried out. Within the scope of the study, 8 compounds were synthesized, and their antioxidant activity was evaluated under in vitro conditions. To establish the mechanism of action, molecular docking was used to model the interaction of the synthesized ligands with the active site of glutathione peroxidase-4 (GPx-4). The conducted analysis revealed key structural features determining antioxidant efficacy and established a correlation between molecular structure and biological activity. The aim . Synthesis, computer screening, and investigation of the antioxidant properties of new azomethines based on sterically hindered phenol, as well as establishing structure–activity relationships. Materials and methods . A new series of 2,6-di-tert-butyl-4-[C-alkyl-(aryl)-(N-phenyl)-azomethine]phenols was synthesized by the condensation of corresponding ketones with aromatic amines in the presence of catalytic amounts of p-toluenesulfonic acid. The structure and purity of the obtained compounds were confirmed by a complex of physicochemical methods, including IR spectroscopy, H NMR spectroscopy, and elemental analysis. For the initial assessment of the biological potency of the synthesized compounds, computer prediction ( in silico ) of their antioxidant, antiradical, and cardiotonic properties was performed using the online platform PASS Online. Molecular modeling of potential inhibitory activity against human glutathione peroxidase-4 (GPx-4) was carried out using the Autodock 4.0 program. The conformational mobility of the ligands was taken into account, for which optimal torsion angles were previously determined and set. Experimental study of antioxidant activity (AOA) was conducted in two model systems: induction of lipid peroxidation (LPO) in a complex of corn oil fatty acids under UV irradiation; and the Fenton system (H₂O₂/Fe²⁺). To compare efficacy, ubiquinone and bottled hydroxytoluene (BHT, the active substance of the drug dibulin), representing the class of sterically hindered phenols, were used as reference standards. Results . The spectrum of biological activity of the studied compounds was predicted in silico using the PASS Online service. As it was expected, all substances have cardiotonic, membrane-stimulating, and antioxidant potential. The presence of AOA and the ability to scavenge free radicals allows these molecules to be classified as antiradical agents. Experimental verification of AOA was carried out in two model systems: based on photooxidation (UV irradiation) of a complex of fatty acids from corn oil (system No. 1) and on the Fenton system (H₂O₂/Fe²⁺, system No. 2). In all the cases, the studied compounds demonstrated high efficacy, inhibiting lipid peroxidation LPO by 42–48%. This result significantly exceeds the activity of standard antioxidants — ubiquinone (11%) and BHT (39%) — in the same conditions. Conclusion . The results of molecular docking indicate a high affinity of the new ligands to the GP-4 protein, with the calculated binding energy for the most promising structures being comparable to that of known standards—ubiquinone, dibulin (hydroxybutylated toluene), and mexidol. In vitro experimental data confirmed the pronounced antioxidant activity of the synthesized compounds. “Lead” structures were identified that surpass classical antioxidants—ubiquinone and dibulin — in efficacy.
- Research Article
78
- 10.1046/j.1523-1747.1998.00405.x
- Dec 1, 1998
- Journal of Investigative Dermatology
Chimeric Human Epidermal Reconstructs to Study the Role of Melanocytes and Keratinocytes in Pigmentation and Photoprotection
- Research Article
72
- 10.1021/acsami.6b08219
- Aug 30, 2016
- ACS Applied Materials & Interfaces
Many conflicting results have been reported related to the antioxidant and oxidant activities of nanoceria. On the basis of this research, many factors might affect the antioxidant activity of nanoceria. However, all of the factors reported only affect the antioxidant activity of nanoceria to a limited extent or cause the antioxidant activity to be lost. We found that several factors can induce conversion between the protective effect and toxicity of nanoceria. At low concentrations of hydroxyl radicals (•OH) and nanomaterials, nanoceria exhibited antioxidant activity but could produce greater amounts of •OH at higher •OH or nanomaterial concentrations and subsequently exhibit oxidant activity. Moreover, the morphology and size of nanoceria can also affect this conversion. We found that high concentrations of •OH and nanoceria could introduce a high amount of Ce(3+) in the system, which might be the reason that nanoceria converted from exhibiting antioxidant to oxidant activity. Under this condition, nanoceria act as a catalyst similar to Fe(2+) to promote •OH production in a Fenton system and also as a catalyst promoter to boost Fe(2+) production of additional •OH during the redox reaction. These conclusions support a better understanding of conflicting reports on medicinal applications for nanoceria and promote their practical application.
- Research Article
26
- 10.17660/actahortic.2008.765.43
- Jan 1, 2008
- Acta Horticulturae
ISHS XXVII International Horticultural Congress - IHC2006: International Symposium on Plants as Food and Medicine: The Utilization and Development of Horticultural Plants for Human Health ANTIOXIDANT ACTIVITY OF THE ESSENTIAL OILS OF THYMBRA CAPITATA, ORIGANUM VULGARE, THYMUS MASTICHINA, AND CALAMINTHA BAETICA
- Research Article
12
- 10.4149/gpb_2009_04_414
- Jan 1, 2009
- General Physiology and Biophysics
Currently, environmental and industrial pollution along with increase and causes multiple stress conditions, the combined exposure to magnetic field and other toxic agents is recognised as an important research area, with a view to better protecting human health against their probable unfavourable effects. In the present study, we investigated the effect of co-exposure to static magnetic field (SMF) and cadmium (Cd) on the antioxidant enzymes activity and the malondialdehyde (MDA) concentration in rat skeletal and cardiac muscles. The exposure of rats to SMF (128 mT, 1 h/day during 30 consecutive days) decreased the activities of glutathione peroxidase (GPx) and the superoxide dismutase (CuZn-SOD) in heart muscle. Sub-chronic exposure to SMF increased the MDA concentration in rat cardiac muscle. Cd treatment (CdCl2, 40 mg/l, per os) during 4 weeks decreased the activities of catalase (CAT) in skeletal muscle and the CuZn-SOD in the heart. Moreover, Cd administration increased MDA concentration in the both structures. The combined effect of SMF (128 mT, 1 h/day during 30 consecutive days) and Cd (40 mg/l, per os) disrupt the antioxidant enzymes activity in rat skeletal and cardiac muscles. Moreover, we noted a huge increase in MDA concentration in the heart and skeletal muscle compared to control group. Thus it is possible that the SMF- and/or Cd-induced depletion of antioxidant enzymes activity in muscle tissues might, like the enhanced lipid peroxidation, importantly contribute to oxidative damage. The combined effect of SMF and Cd altered significantly the antioxidant enzymatic capacity and induced lipid peroxidation in both skeletal and cardiac muscle.
- Research Article
84
- 10.3390/molecules28031043
- Jan 20, 2023
- Molecules
1. Diabetic chronic wounds, mainly foot ulcers, constitute one of the most common complications of poorly managed diabetes mellitus. The most typical reasons are insufficient glycemic management, latent neuropathy, peripheral vascular disease, and neglected foot care. In addition, it is a common cause of foot osteomyelitis and amputation of the lower extremities. Patients are admitted in larger numbers attributable to chronic wounds compared to any other diabetic disease. In the United States, diabetes is currently the most common cause of non-traumatic amputations. Approximately five percent of diabetics develop foot ulcers, and one percent require amputation. Therefore, it is necessary to identify sources of lead with wound-healing properties. Redox imbalance due to excessive oxidative stress is one of the causes for the development of diabetic wounds. Antioxidants have been shown to decrease the progression of diabetic neuropathy by scavenging ROS, regenerating endogenous and exogenous antioxidants, and reversing redox imbalance. Matrix metalloproteinases (MMPs) play vital roles in numerous phases of the wound healing process. Antioxidant and fibroblast cell migration activity of Marantodes pumilum (MP) crude extract has previously been reported. Through their antioxidant, epithelialization, collagen synthesis, and fibroblast migration activities, the authors hypothesise that naringin, eicosane and octacosane identified in the MP extract may have wound-healing properties. 2. The present study aims to identify the bioactive components present in the dichloromethane (DCM) extract of M. pumilum and evaluate their antioxidant and wound healing activity. Bioactive components were identified using LCMS, HPTLC and GCMS. Excision wound on STZ-induced diabetic rat model, human dermal fibroblast (HDF) cell line and colorimetric antioxidant assays were used to evaluate wound healing and antioxidant activities, respectively. Molecular docking and pkCMS software would be utilised to predict binding energy and affinity, as well as ADME parameters. 3. Naringin (NAR), eicosane (EIC), and octacosane (OCT) present in MP displayed antioxidant action and wound excision closure. Histological examination HDF cell line demonstrates epithelialization, collagen production, fibroblast migration, polymorphonuclear leukocyte migration (PNML), and fibroblast movement. The results of molecular docking indicate a substantial attraction and contact between MMPs. pkCMS prediction indicates inadequate blood-brain barrier permeability, low toxicity, and absence of hepatotoxicity. 4. Wound healing properties of (NEO) naringin, eicosane and octacosane may be the result of their antioxidant properties and possible interactions with MMP.
- Research Article
10
- 10.1007/s11746-007-1151-4
- Oct 31, 2007
- Journal of the American Oil Chemists' Society
The antioxidant activities of the raisin extract (RE) in stripped corn oil, stripped corn oil emulsions, and sunflower butter stored at 60 °C for up to 15 days was evaluated. Peroxide values and hexanal content were measured on a half day, 2 or 3 day basis for the emulsion, sunflower butter, and bulk oil, respectively. The RE had the best antioxidant activity in the bulk oil system. Statistical contrasts indicated the oxidation of bulk corn oil treated with RE was significantly (p < 0.001 and p = 0.044) lower than bulk oil and bulk oil treated with tertiary‐butylhydroquinone (TBHQ), respectively. No differences (p = 0.15) in hexanal concentrations were observed in stored bulk oils treated with RE and TBHQ. However, both these materials inhibited hexanal formation better (p < 0.001) when compared to the control corn oil. In contrast, 200 μg/g TBHQ had better (p = 0.0004) antioxidant activity than 3,000 μg/g RE in the oil in water(o/w) emulsion. No significant differences (p = 0.1637) in hexanal formation were observed in the emulsions treated with RE and TBHQ. However, the data indicated that the RE treated emulsion did undergo more secondary oxidation than the emulsion treated with TBHQ beyond 110 h. The 3,000 μg/g RE had antioxidant activity in sunflower butter, but was less effective than the 200 μg/g TBHQ and a lower RE concentration (200 μg/g). The observations supported the hypothesis that RE has antioxidant activity in the multiple model systems.
- Research Article
46
- 10.1016/j.inoche.2010.03.030
- Mar 22, 2010
- Inorganic Chemistry Communications
Evaluation of the antioxidant, DNA interaction and tumor cell cytotoxicity activities of Copper(II) complexes with Paeonol Schiff-base
- Research Article
170
- 10.17221/210/2010-cjfs
- Nov 28, 2011
- Czech Journal of Food Sciences
We described the in vitro antioxidant and antimicrobial activities of ethanol, acetone, and water extracts of beet root pomace. Total contents of phenolics (316.30&ndash;564.50 mg GAE/g of dry extract), flavonoids (316.30&ndash;564.50&nbsp;mg RE/g of dry extract), betacyanins (18.78&ndash;24.18 mg/g of dry extract), and betaxanthins (11.19&ndash;22.90 mg/g of dry extract) after solid-phase extraction were determined spectrophotometrically. The antioxidant activity was determined by measuring the reducing power and DPPH scavenging activity by spectrometric metod, and hydroxyl and superoxide anion radical scavenging activity by ESR spectroscopy. In general, the reducing power of all the beet root pomace extracts increased with increasing concentrations. The DPPH-free radical scavenging activity of the extracts, expressed as EC<sub>50</sub>, ranged from 0.133 mg/ml to 0.275 mg/ml. Significant correlation was observed between all phytochemical components and scavenging activity. 0.5 mg/ml of ethanol extract completely eliminated hydroxyl radical, which had been generated in Fenton system, while the same concentration of this extract scavenged 75% of superoxide anion radicals. In antibacterial tests, Staphylococcus aureus and Bacillus cereus showed higher susceptibility than Escherichia coli and Pseudomonas aeruginosa.
- Research Article
3
- 10.1111/jfbc.13434
- Aug 14, 2020
- Journal of food biochemistry
This study evaluates the antioxidant and antibacterial activity of a mixture of lactoferrin hydrolysate (LfH), whey protein hydrolysate (WPH) and vanillin in vitro and in vivo to design a chemoprotective supplement for reducing the infection and oxidative stress induced by chemotherapy. The designed supplement showed significant antibacterial activity against E. coli. The supplement with the highest concentration exhibited considerable antioxidant activity in (2,2-diphenyl-1-picrylhydrazyl) DPPH free radicals,(2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) ABTS, and reducing power assays. In the biochemical analysis of liver homogenate, the supplement 3 increased the level of enzymes Catalase (CAT), Glutathione peroxidase (GPx), Superoxide dismutase (SOD), and also the Ferric Reducing Ability of Plasma (FRAP) while decreased thiobarbituric acid reactive substances (TBARS) in comparison to paclitaxel group, indicative of activity against oxidative stress. Antibacterial and antioxidant activity of the designed supplement makes it a good candidate for use as a functional food to reduce the side effects of chemotherapy. PRACTICAL APPLICATIONS: A dietary supplement composed of lactoferrin hydrolysate (LfH), whey protein hydrolysate (WPH) and vanillin showed antibacterial activity against E. coli and S. aureus in vitro. The studied supplement also exhibited significant antioxidant properties in the model system and anti-oxidative stress activity in mice exposed to paclitaxel. This supplement has a potential for use in the food matrix to reduce the chemotherapy side effects and to act as a chemoprotective agent.
- Research Article
6
- 10.3760/j:issn:0376-2491.2005.03.011
- Jan 19, 2005
- National Medical Journal of China
To evaluate the effect of laparoscopic surgery on and lipid hyperoxidation in patients with hysteromyoma. Forty patients with hysteromyoma were randomly divided into 2 equal groups: laparoscopy group and laparotomy group. The plasma advanced oxidation protein products (AOPP), malondialdehyde (MDA), antioxidant activity (AOA), and glutathione peroxidase (GPx) activity were measured before operation, just after operation (5 minutes after deflation) and 24 hours after operation. (1) In the laparoscopy group, the levels of AOPP and MDA were (50.20 +/- 9.23) micromol/L and (1.85 +/- 0.19) micromol/L before operation, increased significantly just after operation [(68.75 +/- 12.69) micromol/L and (2.52 +/- 0.55) micromol/L respectively, both P < 0.01], and recovered to the normal level 24 hour postoperatively [(49.70 +/- 9.92) micromol/L and (2.05 +/- 0.68) micromol/L respectively, both P > 0.05]. The levels of GPx and AOA decreased significantly just after operation [(0.29 +/- 0.09) U/ml vs. (0.62 +/- 0.27) U/mL and (0.90 +/- 0.24) mmol/L vs. (1.41 +/- 0.39) mmol/L respectively, both P < 0.01], and the GPx level recovered 24 hours after operation [(0.52 +/- 0.06) U/mL, P > 0.05], however, the AOA level was still lower [(1.00 +/- 0.31) mmol/L, P < 0.01]. In the laparotomy group, the levels of plasma AOPP and MDA level slightly increased just after operation in comparison with those before operation [(53.39 +/- 9.86) micromol/L vs. (52.30 +/- 7.10) micromol/L and (2.09 +/- 0.51) micromol/L vs. (1.83 +/- 0.64) micromol/L respectively, both P > 0.05] and continued to increase 24 hours after operation [(63.40 +/- 15.5) micromol/L, P < 0.05, and (2.42 +/- 0.44) micromol/L, P < 0.01]; the GPx and AOA levels decreased a little just after operation [(0.51 +/- 0.17) U/mL vs. (0.57 +/- 0.21) U/mL and (1.20 +/- 0.46) mmol/L vs. (1.33 +/- 0.37) mmol/L, both P > 0.05] and continued to decrease 24 hours after operation [(0.35 +/- 0.19) U/mL and (0.92 +/- 0.22) mmol/L respectively, both P < 0.01]. Compared with those of the laparotomy group, the plasma AOPP and MDA levels of the laparoscopy group were both significantly lower (P < 0.01 and P < 0.05), and the GPx level was significantly higher (P < 0.01) 24 hours after operation, however, the AOA level was not significantly different (P > 0.05). Laparoscopic surgery is better than laparotomy. Protein oxidation and lipid hyperoxidation occur during the laparoscopic surgery, however, disappeared after operation. Free radicals are generated by the end of laparoscopic procedure, possibly as a result of an ischemia-reperfusion phenomenon induced by the inflation and deflation of the pneumoperitoneum. AOPP and MDA are induced during laparoscopic procedure and then return to the normal levels finally.
- Research Article
133
- 10.1016/j.phymed.2012.12.005
- Jan 23, 2013
- Phytomedicine
Neuroprotective effects of inhaled lavender oil on scopolamine-induced dementia via anti-oxidative activities in rats
- Research Article
57
- 10.1016/j.theriogenology.2010.01.007
- Mar 12, 2010
- Theriogenology
Cryopreservation of epididymal cat spermatozoa: effects of in vitro antioxidative enzymes supplementation and lipid peroxidation induction
- Research Article
2
- 10.1016/j.ijbiomac.2025.144051
- Jun 1, 2025
- International journal of biological macromolecules
Novel exopolysaccharide from Limosilactobacillus fermentum A10: Biosynthesis, physicochemical properties and antioxidant activity.
- Research Article
12
- 10.2147/dddt.s489113
- Mar 1, 2025
- Drug design, development and therapy
Diabetic wounds are a significant clinical challenge due to impaired healing processes often exacerbated by elevated matrix metalloproteinases (MMPs). Cinnamomum zeylanicum, known for its anti-inflammatory and antioxidant properties, has shown potential in promoting wound healing. This study investigates the molecular docking and experimental validation of Cinnamomum zeylanicum's effects on diabetic wound healing, focusing on its interaction with matrix metalloproteinases-8 (MMP-8) and 9 (MMP-9). Molecular docking studies were performed to predict the binding affinity of Cinnamomum zeylanicum compounds to MMP-8 and MMP-9. Diabetic wound healing was evaluated using in vivo models where wounds were induced and treated with Cinnamomum zeylanicum extract. Various parameters were measured, including wound contraction, hydroxyproline content, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels. Biochemical analyses included glucose levels, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), and histomorphological examination of skin tissues. Molecular docking results indicated a high binding affinity of Cinnamomum zeylanicum's bioactive compounds with MMP-8 and MMP-9, suggesting potential inhibition. Experimental validation showed significant improvement in wound contraction and increased hydroxyproline content, indicating enhanced collagen synthesis. Antioxidant enzyme activities (SOD, GPx, CAT) were significantly elevated, while MDA levels were reduced, reflecting decreased oxidative stress. Biochemical analysis demonstrated improved glucose homeostasis with reduced FBG and enhanced OGTT responses. Histomorphological studies revealed improved tissue architecture and re-epithelialization in treated wounds. Cinnamomum zeylanicum exhibits promising potential in diabetic wound healing by modulating MMP-8 and MMP-9 activities, enhancing antioxidant defenses, and improving glucose regulation. These findings support its therapeutic application for diabetic wounds, providing a foundation for further clinical investigations.
- Research Article
6
- 10.3746/jkfn.2009.38.1.019
- Jan 31, 2009
- Journal of the Korean Society of Food Science and Nutrition
식용 및 약용으로 예로부터 널리 이용하는 양송이버섯 추출물의 생리적 기능에 대한 활성을 탐색하기 위하여 양송이 버섯(Agaricus bisporus)의 에탄올 추출물의 항산화 효과와 Ames test를 통한 돌연변이 유발 억제능을 탐색하였다. 지질과산화물에 대한 단백질 보호효과를 알아본 결과, 양송이 버섯 에탄올 추출물은 MDA와 BSA의 교차결합 형성을 100㎎/assay이었을 때 72.21% 저해하였다. Fe²?에 의해 유도된 지질의 과산화에 대한 저해율은 2.0 ㎎/assay일 때 24.96%였으며, DPPH 라디칼 소거 활성을 측정한 결과 1.0 ㎎/assay일 때 52.75%의 저해율을 보였으며 처리농도가 증가할 수록 저해율은 증가하였다. IC?? 값으로 항산화능의 상대적 비교를 하였을 때 양송이버섯 추출물은 DPPH 라디칼 소거활성이 가장 강하였으며, 그 다음은 지질과산화 억제능이었고 MDA와 BSA의 교차결합 억제능이 가장 낮았다. Ames test를 이용하여 돌연변이 유발 억제능을 알아본 결과, 양송이버섯 에탄올 추출물은 Salmonella Typhimurium TA98 및 TA100 두 균주에서 직접작용 돌연변이능을 각각 100% 저해하여 매우 효과적이었다. 간접작용 돌연변이능 저해효과는 Salmonella Typhimurium TA98에서 86.09%, Salmonella Typhimurium TA100에서는 81.93%로 나타나 양송이버섯 에탄올 추출물은 직접, 간접작용 돌연변이능에 대한 저해효과가 우수하다고 사료된다. 본 연구 결과를 종합해 볼 때, 양송이버섯은 항산화성과 항돌연변이성이 우수하므로 기능성식품으로 개발할 수 있는 가능성이 있다고 본다.