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1.
Anal Biochem ; 695: 115632, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39089362

ABSTRACT

This study aims to quantify haloperidol and methylparaben in a liquid pharmaceutical formulation (2 mg/ml) using UV spectrometry and the simultaneous equations method. Additionally, we explored the stability of haloperidol under various stress conditions. The UV analysis revealed maximum absorption peaks at 248 nm for haloperidol and 256 nm for methylparaben, using a 1 % (v/v) lactic acid solution as the solvent. Method validation, conducted according to ICH guidelines, affirmed the method's reliability, showing excellent results in terms of linearity, precision, accuracy, and sensitivity. The method allows direct application to finished products, enabling simultaneous quantification without extractions. Its simplicity, speed, and cost-effectiveness make it ideal for routine controls in pharmaceutical industry haloperidol solution analyses. The method extends to monitoring forced degradation, indicating photolytic and hydrolytic degradation under acidic and basic conditions, while affirming thermal and oxidative stability. This proposed UV spectrometric method serves as a compelling alternative to pharmacopeia-recommended techniques, simplifying simultaneous determination of the active ingredient and preservative. This streamlines analysis, reducing time and costs. Additionally, it proves valuable in small industries lacking sophisticated instrumentation, offering insights into active ingredient behavior during forced degradation.


Subject(s)
Haloperidol , Parabens , Spectrophotometry, Ultraviolet , Haloperidol/analysis , Haloperidol/chemistry , Parabens/analysis , Parabens/chemistry , Drug Stability
2.
Environ Res ; 258: 119477, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38909943

ABSTRACT

In this study, UiO-67 (Zr)/g-C3N4 composites (U67N) were synthesized at wt.% ratios of 05:95, 15:85, and 30:70 using the solvothermal method at 80 °C for 24 h followed by calcination at 350 °C. The composites were characterized using UV-Vis diffuse reflectance spectroscopy, Fourier-transform infrared spectroscopy, photoluminescence spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, scanning electron microscopy-energy-dispersive X-ray spectroscopy, transmission electron microscopy, and nitrogen physisorption analysis. In addition, thermal stability analysis of UiO-67 was conducted using thermogravimetric analysis. The photocatalytic performance of the composites was assessed during the degradation and mineralization of a mixture of methylparaben (MeP) and propylparaben (PrP) under simulated sunlight. The adsorption process of U67N 15:85 was characterized through kinetic studies and adsorption capacity experiments, which were modeled using pseudo-first-order and pseudo-second-order kinetics and Langmuir and Freundlich isotherms, respectively. The influence of pH levels 3, 5, and 7 on the photocatalytic degradation of the mixture was investigated, revealing enhanced degradation and mineralization at pH 3. The U67N composite exhibited dual capability in removing contaminants through adsorption and photocatalytic processes. Among the prepared composites, U67N 15:85 demonstrated the highest photocatalytic activity, achieving removal efficiencies of 96.8% for MeP, 92.5% for PrP, and 45.7% for total organic carbon in 300 kJ/m2 accumulated energy (3 h of reaction time). The detoxification of the effluent was confirmed through acute toxicity evaluation using the Vibrio fischeri method. The oxidation mechanism of the heterojunction formed between UiO-67 (Zr) and g-C3N4 was proposed based on PL analysis, photoelectrochemistry studies (including photocurrent response, Nyquist, and Mott-Schottky analyses), and scavenger assays.


Subject(s)
Parabens , Water Pollutants, Chemical , Parabens/chemistry , Adsorption , Water Pollutants, Chemical/chemistry , Metal-Organic Frameworks/chemistry , Catalysis , Kinetics
3.
Arch Toxicol ; 98(2): 571-575, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38052763

ABSTRACT

Hazardous properties of a large number of esters of 4-hydroxybenzoic acid (parabens) have been proposed by ECHA to be assessed as a group. We recommend to restrict the grouping approach to short chain esters, i.e. methyl, ethyl, propyl and butyl paraben which are very similar in chemical structures, physicochemical properties, toxicokinetics, and hazardous properties. While these parabens show a weak estrogenicity in some in vitro or in vivo screening assays, they do not induce estrogen-receptor-mediated adverse effects in intact animals. Therefore, there is no support regarding classification and labeling of endocrine disruption or reproductive toxicity of these parabens.


Subject(s)
Esters , Parabens , Animals , Parabens/toxicity , Parabens/chemistry , Esters/toxicity , Endocrine System , Receptors, Estrogen
4.
Biofouling ; 40(3-4): 245-261, 2024.
Article in English | MEDLINE | ID: mdl-38639133

ABSTRACT

Pathogenic bacteria in drinking-water pose a health risk to consumers, as they compromise the quality of portable water. Chemical disinfection of water containing dissolved organic matter (DOM) causes harmful disinfection by-products. In this work, 4-hydroxybenzoic acid (4-HBA) blended polyethersulfone membranes were fabricated and characterised using microscopic and spectroscopic techniques. The membranes were evaluated for the removal of bacteria and DOM from synthetic and environmental water. Permeate flux increased from 287.30 to 374.60 l m-2 h-1 at 3 bars when 4-HBA increased from 0 to 1.5 wt.%, suggesting that 4-HBA influenced the membrane's affinity for water. Furthermore, 4-HBA demonstrated antimicrobial properties by inhibiting bacterial growth. The membrane with 1 wt.% 4-HBA recorded 99.4 and 100% bacteria removal in synthetic and environmental water, respectively. Additionally, DOM removal of 55-73% was achieved. A flux recovery ratio (FRR) of 94.6% was obtained when a mixture of bacteria and humic acid was filtered, implying better fouling layer reversibility during cleaning. Furthermore, 100% FRR was achieved when a multimedia granular filtration step was installed prior to membrane filtration. The results illustrated that the membranes had a high permeate flux with low irreversible fouling. This indicated the potential of the membranes in treating complex feed streams using simple cleaning protocols.


Subject(s)
Bacteria , Biofilms , Biofouling , Fresh Water , Membranes, Artificial , Water Purification , Biofilms/drug effects , Biofilms/growth & development , Biofouling/prevention & control , Water Purification/methods , Fresh Water/microbiology , Bacteria/drug effects , Humic Substances/analysis , Filtration/methods , Parabens/chemistry , Sulfones/chemistry , Polymers/chemistry
5.
Molecules ; 29(19)2024 Sep 26.
Article in English | MEDLINE | ID: mdl-39407502

ABSTRACT

An eco-friendly method for the determination of sweeteners (aspartame, acesulfame-K) and preservatives (benzoic acid, sorbic acid, methylparaben, ethylparaben) in functional beverages and flavoured waters using thin film microextraction (TFME) and high-performance liquid chromatography with UV detection (HPLC-UV) was proposed. A series of fourteen green and renewable solidified natural deep eutectic solvents (NADESs) were prepared and tested as 'eutectosorbents' in TFME for the first time. In the proposed method, the NADES containing acetylcholine chloride and 1-docosanol at a 1:3 molar ratio was finally chosen to coat a support. Four factors, i.e., the mass of the NADES, pH of the samples, extraction time, and desorption time, were tested in the central composite design to select the optimal TFME conditions. Limits of detection were equal to 0.022 µg mL-1 for aspartame, 0.020 µg mL-1 for acesulfame-K, 0.018 µg mL-1 for benzoic acid, 0.026 µg mL-1 for sorbic acid, 0.013 µg mL-1 for methylparaben, and 0.011 µg mL-1 for ethylparaben. Satisfactory extraction recoveries between 82% and 96% were achieved with RSDs lower than 6.1% (intra-day) and 7.4% (inter-day). The proposed 'eutectosorbent' presented good stability that enabled effective extractions for 16 cycles with recovery of at least 77%. The proposed NADES-TFME/HPLC-UV method is highly sensitive and selective. However, the use of a solid NADES as a sorbent, synthesized without by-products, without the need for purification, and with good stability on a support with the possibility of reusability increases the ecological benefit of this method. The greenness aspect of the method was evaluated using the Complex modified Green Analytical Procedure Index protocol and is equal to 84/100.


Subject(s)
Beverages , Sweetening Agents , Sweetening Agents/chemistry , Sweetening Agents/analysis , Sweetening Agents/isolation & purification , Chromatography, High Pressure Liquid/methods , Beverages/analysis , Deep Eutectic Solvents/chemistry , Solid Phase Microextraction/methods , Liquid Phase Microextraction/methods , Parabens/analysis , Parabens/chemistry , Parabens/isolation & purification , Food Preservatives/chemistry , Food Preservatives/analysis , Aspartame/analysis , Aspartame/chemistry , Water/chemistry
6.
Water Sci Technol ; 89(12): 3178-3191, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39150419

ABSTRACT

The radiolytic degradation of 4-hydroxybenzoate (4-HBA-) in aerated, oxygen-free and N2O-saturated aqueous solutions at concentrations of 0.10 and 0.25 mmol/dm3 were gamma irradiated at different doses in a source of Co-60. The results show that ·OH adds predominantly to the 3 position of the aromatic ring, and elimination of the acid group leads to the degradation of 4-HBA-. With an N2O-saturated 0.10 mmol/dm3 4-HBA- solution, total degradation occurred at 1.6 kGy, and with a 0.25 mmol/dm3 solution, total degradation occurred at 3.5 kGy. In the aerated and oxygen-free 0.25 mmol/dm3 4-HBA- solutions, the behavior was similar, degradation occurring at a dose of 13.1 kGy. At the concentration of 0.10 mmol/dm3, total degradation occurred at 7.0 kGy, with small amounts of radiolytic products and byproducts. We propose a mechanism for the degradation of 4-HBA- caused by water radicals produced in the three environments, leading to formation of the identified stable products. Oxidation was followed by chemical oxygen demand (COD), which decreased as the 4-HBA- concentration increased. The kinetics showed a pseudo-first-order behavior. The rate constant of degradation was similar for the solutions with and without oxygen.


Subject(s)
Oxygen , Parabens , Parabens/chemistry , Oxygen/chemistry , Gamma Rays , Water Pollutants, Chemical/chemistry , Water/chemistry , Solutions
7.
J Am Acad Dermatol ; 87(5): 1081-1086, 2022 11.
Article in English | MEDLINE | ID: mdl-34144080

ABSTRACT

BACKGROUND: Product disclaimers listed on personal care products face limited regulation. These disclaimers may be helpful or may mislead the public. OBJECTIVE: Review the evidence supporting the potential harms of 3 compounds commonly addressed by product disclaimers: parabens, aluminum, and sulfates. METHODS: Reported cases of adverse events to these compounds were identified. Trends in allergic contact dermatitis reactions to chemicals used in place of these compounds were also identified. RESULTS: There is limited evidence that parabens and aluminum pose a threat to human health; there is even less evidence that topical sulfate-containing products pose a danger to consumers. In the setting of paraben avoidance, there has been a steady increase in cases of allergic contact dermatitis to preservatives that are more allergenic, specifically the isothiazolinones. LIMITATIONS: Assessment of the toxicology of these compounds is ongoing and may change with new data. CONCLUSION: There is limited evidence that parabens, aluminum, and sulfates used in personal care products pose a health risk. There is evidence that avoidance of parabens has resulted in an epidemic of allergic contact dermatitis to isothiazolonine preservatives.


Subject(s)
Cosmetics , Dermatitis, Allergic Contact , Aluminum/adverse effects , Cosmetics/adverse effects , Cosmetics/chemistry , Dermatitis, Allergic Contact/epidemiology , Dermatitis, Allergic Contact/etiology , Humans , Parabens/adverse effects , Parabens/chemistry , Preservatives, Pharmaceutical/adverse effects , Sulfates
8.
Regul Toxicol Pharmacol ; 132: 105161, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35508214

ABSTRACT

Parabens are esters of para-hydroxybenzoic acid that have been used as preservatives in many types of products for decades including agrochemicals, pharmaceuticals, food and cosmetics. This illustrative case study with propylparaben (PP) demonstrates a 10-step read-across (RAX) framework in practice. It aims at establishing a proof-of-concept for the value added by new approach methodologies (NAMs) in read-across (RAX) for use in a next-generation risk assessment (NGRA) in order to assess consumer safety after exposure to PP-containing cosmetics. In addition to structural and physico-chemical properties, in silico information, toxicogenomics, in vitro toxicodynamic, toxicokinetic data from PBK models, and bioactivity data are used to provide evidence of the chemical and biological similarity of PP and analogues and to establish potency trends for observed effects in vitro. The chemical category under consideration is short (C1-C4) linear chain n-alkyl parabens: methylparaben, ethylparaben, propylparaben and butylparaben. The goal of this case study is to illustrate how a practical framework for RAX can be used to fill a hypothetical data gap for reproductive toxicity of the target chemical PP.


Subject(s)
Cosmetics , Parabens , Cosmetics/chemistry , Cosmetics/toxicity , Parabens/chemistry , Parabens/toxicity , Preservatives, Pharmaceutical/toxicity , Reproduction , Risk Assessment/methods
9.
Molecules ; 27(13)2022 Jul 01.
Article in English | MEDLINE | ID: mdl-35807508

ABSTRACT

Parabens (PBs) are used as preservatives to extend the shelf life of various foodstuffs, and pharmaceutical and cosmetic preparations. In this work, the membrane barrier passage potential of a subset of seven parabens, i.e., methyl-, ethyl-, propyl- isopropyl, butyl, isobutyl, and benzyl paraben, along with their parent compound, p-hydroxy benzoic acid, were studied. Thus, the Franz cell diffusion (FDC) method, biomimetic liquid chromatography (BLC), and in silico prediction were performed to evaluate the soundness of both describing their permeation through the skin. While BLC allowed the achievement of a full scale of affinity for membrane phospholipids of the PBs under research, the permeation of parabens through Franz diffusion cells having a carbon chain > ethyl could not be measured in a fully aqueous medium, i.e., permeation enhancer-free conditions. Our results support that BLC and in silico prediction alone can occasionally be misleading in the permeability potential assessment of these preservatives, emphasizing the need for a multi-technique and integrated experimental approach.


Subject(s)
Parabens , Skin Absorption , Biomimetics , Chromatography, Liquid , Parabens/chemistry , Preservatives, Pharmaceutical/chemistry
10.
Mol Microbiol ; 114(5): 870-886, 2020 11.
Article in English | MEDLINE | ID: mdl-32757400

ABSTRACT

Xanthomonas campestris pv. campestris (Xcc) is the causal agent of black rot in crucifers. Our previous findings revealed that Xcc can degrade 4-hydroxybenzoic acid (4-HBA) via the ß-ketoadipate pathway. This present study expands on this knowledge in several ways. First, we show that infective Xcc cells induce in situ biosynthesis of 4-HBA in host plants, and Xcc can efficiently degrade 4-HBA via the pobA/pobR locus, which encodes a 4-hydroxybenzoate hydroxylase and an AraC-family transcription factor respectively. Next, the transcription of pobA is specifically induced by 4-HBA and is positively regulated by PobR, which is constitutively expressed in Xcc. 4-HBA directly binds to PobR dimers, resulting in activation of pobA expression. Point mutation and subsequent isothermal titration calorimetry and size exclusion chromatography analysis identified nine key conserved residues required for 4-HBA binding and/or dimerization of PobR. Furthermore, overlapping promoters harboring fully overlapping -35 elements were identified between the divergently transcribed pobA and pobR. The 4-HBA/PobR dimer complex specifically binds to a 25-bp site, which encompasses the -35 elements shared by the overlapping promoters. Finally, GUS histochemical staining and subsequent quantitative assay showed that both pobA and pobR genes are transcribed during Xcc infection of Chinese radish, and the strain ΔpobR exhibited compromised virulence in Chinese radish. These findings suggest that the ability of Xcc to survive the 4-HBA stress might be important for its successful colonization of host plants.


Subject(s)
Parabens/metabolism , Xanthomonas campestris/genetics , Xanthomonas campestris/metabolism , AraC Transcription Factor/genetics , Bacterial Proteins/metabolism , DNA, Bacterial/metabolism , Gene Expression Regulation, Bacterial/genetics , Parabens/chemistry , Trans-Activators/metabolism , Transcription Factors/metabolism , Virulence/genetics , Xanthomonas campestris/pathogenicity
11.
J Sep Sci ; 44(2): 549-556, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33191605

ABSTRACT

A visual, rapid, and sensitive micro-solid phase extraction method was developed for the detection of p-hydroxybenzoic acid using molecularly imprinted chitosan microspheres based on deep eutectic solvents, both as a functional monomer and template. The parameters were optimized by using the response surface methodology strategy. The extraction capacity of p-hydroxybenzoic acid from pear rind under the optimized conditions using response surface methodology was 46.32 mg/g, when the pH of the extract solution (2), extraction time (35 min), extraction temperature (30°C), and adsorbent dosage (2 mg). The molecularly imprinted chitosan microspheres produced higher selectivity and extraction capacity than the traditional materials.


Subject(s)
Chitosan/chemistry , Microspheres , Molecular Imprinting , Parabens/isolation & purification , Pyrus/chemistry , Solid Phase Extraction , Adsorption , Hydrogen-Ion Concentration , Parabens/chemistry , Particle Size , Solvents/chemistry , Temperature
12.
Arch Toxicol ; 95(3): 853-881, 2021 03.
Article in English | MEDLINE | ID: mdl-33459807

ABSTRACT

This article presents the outcomes of higher-tier repeated-dose toxicity studies and developmental and reproductive toxicity (DART) studies using Wistar rats requested for methyl paraben and propyl paraben under the European Union chemicals legislation. All studies revealed no-observed adverse effects (NOAELs) at 1000 mg/kg body weight/day. These findings (absence of effects) were then used to interpolate the hazard profile for ethyl paraben, further considering available data for butyl paraben. The underlying read-across hypothesis (all shorter-chained linear n-alkyl parabens are a 'category' based on very high structural similarity and are transformed to a common compound) was confirmed by similarity calculations and comparative in vivo toxicokinetics screening studies for methyl paraben, ethyl paraben, propyl paraben and butyl paraben. All four parabens were rapidly taken up systemically following oral gavage administration to rats, metabolised to p-hydroxybenzoic acid, and rapidly eliminated (parabens within one hour; p-hydroxybenzoic acid within 4-8 h). Accordingly, for ethyl paraben, the NOAELs for repeated-dose toxicity and DART were interpolated to be 1000 mg/kg body weight/day. Finally, all evidence was evaluated to address concerns expressed in the literature that parabens might be endocrine disruptors. This evaluation showed that the higher-tier studies do not provide any indication for any endocrine disrupting property. This is the first time that a comprehensive dataset from higher-tier in vivo studies following internationally agreed test protocols has become available for shorter-chained linear n-alkyl parabens. Consistently, the dataset shows that these parabens are devoid of repeated-dose toxicity and do not possess any DART or endocrine disrupting properties.


Subject(s)
Endocrine Disruptors/toxicity , Parabens/toxicity , Animals , Dose-Response Relationship, Drug , Endocrine Disruptors/administration & dosage , Endocrine Disruptors/chemistry , Female , Male , No-Observed-Adverse-Effect Level , Parabens/administration & dosage , Parabens/chemistry , Rats , Rats, Wistar , Time Factors , Toxicokinetics
13.
Regul Toxicol Pharmacol ; 122: 104918, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33741472

ABSTRACT

Parabens are antimicrobial compounds used as preservatives in cosmetics, foods, and pharmaceuticals. Paraben exposure occurs through a variety of routes including dermal absorption, ingestion, and inhalation. Ester bond hydrolysis has been shown to be the predominant biotransformation for this chemical class. Here we evaluated a series of parabens of increasing alkyl chain length and branching in addition to the aryl side chain of phenyl paraben (PhP). We evaluated the parabens under full Michaelis-Menten (MM) parameters to obtain intrinsic clearance values and found different trends between human liver and skin, which correlate with the predominant esterase enzymes in those matrices, respectively. In liver, where carboxylesterase 1 (CES1) is the predominant esterase enzyme, the shorter chain parabens were more readily metabolized, while in skin, where carboxylesterase 2 (CES2) is the predominant esterase enzyme, the longer chain parabens were more readily metabolized. Alkyl chain branching reduced the hydrolysis rates relative to those for the straight chain compounds, while the addition of a phenyl group, as in PhP, showed an increase in hydrolysis, producing the highest observed hydrolysis rate for skin. These data summarize the structure-metabolism relationship for a series of parabens and contribute to the safety assessment of this class of compounds.


Subject(s)
Parabens/chemistry , Parabens/pharmacology , Preservatives, Pharmaceutical/chemistry , Preservatives, Pharmaceutical/pharmacology , Blood/drug effects , Esterases/metabolism , Female , Humans , Liver/drug effects , Male , Skin/drug effects
14.
Biomed Chromatogr ; 35(10): e5152, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33931875

ABSTRACT

A stability-indicating HPLC method was developed for the simultaneous determination of paraben mixture and its degradation products in effervescent potassium chloride tablets. The chromatographic separation was achieved on a Waters Cortecs C18 column (2.7 µm, 4.6 × 150 mm) using gradient elution. The optimized mobile phase consisted of 0.1% orthophosphoric acid in purified water as solvent A and purified water, acetonitrile, and orthophosphoric acid (100:900:1, v/v) as solvent B. The flow rate was 0.8 mL/min, and column temperature was maintained at 35°C. The injection volume was 10 µL, and UV detection was carried out at 254 nm. The selectively developed method has optimal separation among p-hydroxybenzoic acid, methylparaben, ethylparaben, propylparaben, and butylparaben peaks in the presence of specified and unspecified degradation products in the determination of drug product. The mass balance obtained from forced degradation studies was ≥95% and thus proves the stability-indicating property of the developed method. The developed reversed-phase HPLC method has been validated according to the International Conference on Harmonization guidelines. The correlation coefficients for all the peaks were >0.9999. The results of the other validation parameters were found within the limits. Finally, the optimized method was used in the quality control lab for stability analysis.


Subject(s)
Chromatography, High Pressure Liquid/methods , Parabens , Chromatography, Reverse-Phase , Drug Stability , Limit of Detection , Linear Models , Parabens/analysis , Parabens/chemistry , Potassium Chloride/chemistry , Reproducibility of Results , Tablets
15.
Biomed Chromatogr ; 35(2): e4974, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32893361

ABSTRACT

An improved fabric-phase sorptive extraction (FPSE) protocol has been developed and validated herein for the simple, fast, sensitive and green determination of seven parabens-methyl paraben, ethyl paraben, propyl paraben, butyl paraben, isopropyl paraben, isobutyl paraben and benzyl paraben-in human urine samples by HPLC-DAD. The mobile phase consisted of ammonium acetate (0.05 m) and acetonitrile, while total analysis time was 13.2 min. Sol-gel poly (tetrahydrofuran) coated FPSE membrane resulted in optimum extraction sensitivity for the seven parabens. The novel FPSE medium as well as the improved and faster sample preparation procedure resulted in lower limit of detection and quantitation values in comparison with previously reported methods. The separation was carried out using an RP-HPLC method with a Spherisorb C18 column and a flow rate of 1.4 ml/min. The validation of the analytical method was carried out by means of linearity, precision, accuracy, selectivity, sensitivity and robustness. For all seven parabens, the limits of detection and quantitation were 0.003 and 0.01 µg/ml, respectively. Relative recovery rates were between 86.3 and 104%, while RSD values were <12.6 and 19.3% for within- and between-day repeatability, respectively. The method was subsequently applied to real human urine samples.


Subject(s)
Chemical Fractionation/methods , Chromatography, High Pressure Liquid/methods , Parabens/analysis , Humans , Limit of Detection , Linear Models , Parabens/chemistry , Parabens/isolation & purification , Reproducibility of Results , Textiles
16.
Molecules ; 26(9)2021 May 01.
Article in English | MEDLINE | ID: mdl-34062815

ABSTRACT

Aza-porphyrinoids exhibit distinct spectral properties in UV-Vis, and they are studied in applications such as photosensitizers in medicine and catalysts in technology. The use of appropriate peripheral substituents allows the modulation of their physicochemical properties. Phthalocyanine and sulfanyl porphyrazine octa-substituted with 4-(butoxycarbonyl)phenyloxy moieties were synthesized and characterized using UV-Vis and NMR spectroscopy, as well as mass spectrometry. A comparison of porphyrazine with phthalocyanine aza-porphyrinoids revealed that phthalocyanine macrocycle exhibits higher singlet oxygen generation quantum yields, reaching the value of 0.29 in DMF. After both macrocycles had been deposited on titanium dioxide nanoparticles P25, the cytotoxicities and photocytotoxicities of the prepared materials were studied using a Microtox® acute toxicity test. The highest cytotoxicity occurred after irradiation with a red light for the material composed of phthalocyanine deposited on titania nanoparticles.


Subject(s)
Indoles/chemistry , Metal Nanoparticles/chemistry , Parabens/chemistry , Porphyrins/chemistry , Titanium/chemistry , Anti-Infective Agents/administration & dosage , Antineoplastic Agents/administration & dosage , Cell Survival , Drug Design , Isoindoles , Magnetic Resonance Spectroscopy , Nanomedicine/methods , Nanoparticles/chemistry , Neoplasms/drug therapy , Particle Size , Photosensitizing Agents/chemistry , Singlet Oxygen/chemistry , Solvents , Toxicity Tests , Ultraviolet Rays
17.
Molecules ; 26(15)2021 Jul 30.
Article in English | MEDLINE | ID: mdl-34361795

ABSTRACT

Although Australia is the largest exporter of faba bean globally, there is limited information available on the levels of bioactive compounds found in current commercial faba bean varieties grown in this country. This study profiled the phenolic acid and flavonoid composition of 10 Australian faba bean varieties, grown at two different locations. Phenolic profiling by HPLC-DAD revealed the most abundant flavonoid to be catechin, followed by rutin. For the phenolic acids, syringic acid was found in high concentrations (72.4-122.5 mg/kg), while protocatechuic, vanillic, p-hydroxybenzoic, chlorogenic, p-coumaric, and trans-ferulic acid were all found in low concentrations. The content of most individual phenolics varied significantly with the variety, while some effect of the growing location was also observed. This information could be used by food processors and plant breeders to maximise the potential health benefits of Australian-grown faba bean.


Subject(s)
Antioxidants/chemistry , Crops, Agricultural/chemistry , Flavonoids/chemistry , Vicia faba/chemistry , Antioxidants/classification , Antioxidants/isolation & purification , Australia , Catechin/chemistry , Catechin/isolation & purification , Chlorogenic Acid/chemistry , Chlorogenic Acid/isolation & purification , Chromatography, High Pressure Liquid/methods , Coumaric Acids/chemistry , Coumaric Acids/isolation & purification , Crops, Agricultural/growth & development , Crops, Agricultural/metabolism , Flavonoids/classification , Flavonoids/isolation & purification , Gallic Acid/analogs & derivatives , Gallic Acid/chemistry , Gallic Acid/isolation & purification , Humans , Hydroxybenzoates/chemistry , Hydroxybenzoates/isolation & purification , Parabens/chemistry , Parabens/isolation & purification , Rutin/chemistry , Rutin/isolation & purification , Vanillic Acid/chemistry , Vanillic Acid/isolation & purification , Vicia faba/growth & development , Vicia faba/metabolism
18.
Molecules ; 26(16)2021 Aug 14.
Article in English | MEDLINE | ID: mdl-34443516

ABSTRACT

Oxidative stress and inflammation are two conditions that coexist in many multifactorial diseases such as atherosclerosis and neurodegeneration. Thus, the design of multifunctional compounds that can concurrently tackle two or more therapeutic targets is an appealing approach. In this study, the basic NSAID structure was fused with the antioxidant moieties 3,5-di-tert-butyl-4-hydroxybenzoic acid (BHB), its reduced alcohol 3,5-di-tert-butyl- 4-hydroxybenzyl alcohol (BHBA), or 6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid (Trolox), a hydrophilic analogue of α-tocopherol. Machine learning algorithms were utilized to validate the potential dual effect (anti-inflammatory and antioxidant) of the designed analogues. Derivatives 1-17 were synthesized by known esterification methods, with good to excellent yields, and were pharmacologically evaluated both in vitro and in vivo for their antioxidant and anti-inflammatory activity, whereas selected compounds were also tested in an in vivo hyperlipidemia protocol. Furthermore, the activity/binding affinity of the new compounds for lipoxygenase-3 (LOX-3) was studied not only in vitro but also via molecular docking simulations. Experimental results demonstrated that the antioxidant and anti-inflammatory activities of the new fused molecules were increased compared to the parent molecules, while molecular docking simulations validated the improved activity and revealed the binding mode of the most potent inhibitors. The purpose of their design was justified by providing a potentially safer and more efficient therapeutic approach for multifactorial diseases.


Subject(s)
Antioxidants/chemistry , Atherosclerosis/drug therapy , Hyperlipidemias/drug therapy , Inflammation/drug therapy , Lipoxygenase Inhibitors/chemistry , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Antioxidants/chemical synthesis , Antioxidants/pharmacology , Atherosclerosis/pathology , Chromans/chemistry , Chromans/pharmacology , Drug Design , Humans , Hyperlipidemias/pathology , Hypolipidemic Agents/chemical synthesis , Hypolipidemic Agents/chemistry , Hypolipidemic Agents/pharmacology , Inflammation/pathology , Lipoxygenase/chemistry , Lipoxygenase/drug effects , Lipoxygenase Inhibitors/chemical synthesis , Lipoxygenase Inhibitors/pharmacology , Molecular Docking Simulation , Nerve Degeneration/drug therapy , Nerve Degeneration/pathology , Oxidative Stress/drug effects , Parabens/chemistry , Parabens/pharmacology , Structure-Activity Relationship
19.
Biochem Biophys Res Commun ; 525(3): 720-725, 2020 05 07.
Article in English | MEDLINE | ID: mdl-32143826

ABSTRACT

Microbacterium hydrocarbonoxydans was isolated, using hydrazide compounds as its sole carbon source. The key enzyme that metabolizes these compounds was identified as hydrazidase, and the operon containing the gene coding for the enzyme, was revealed by genome sequencing. The operon also contained genes coding for an ATP-binding cassette transporter (ABC transporter), which was expected to transport the hydrazide compounds. Substrate binding protein (SBP), a component subunit of the transporter, plays an important role in recognizing the correct substrates for transport. Therefore, to elucidate the mechanism of recognition of the unnatural hydrazide compounds, we determined the crystal structures of the SBP, obtained from M. hydrocarbonoxydans (Mh-SBP), complexed with and without the hydrazide compound, at 2.2 Å and 1.75 Å resolutions, respectively. The overall structures of Mh-SBP were similar to those of the SBP in oligopeptide transporters such as OppA. On comparison, the liganded and unliganded structures of Mh-SBP showed an open - close conformation change. Interestingly, the binding mode of the compound to Mh-SBP was almost identical to that of the compound to hydrazidase, suggesting that the ABC transporter served transporting these compounds. Furthermore, based on the hydrazide complex structure, paraben, the other putative substrate of the protein, was successfully used with Mh-SBP to obtain the paraben complex structure.


Subject(s)
Actinobacteria/metabolism , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Hydrazines/metabolism , Membrane Transport Proteins/chemistry , Membrane Transport Proteins/metabolism , Ligands , Microbacterium , Models, Molecular , Parabens/chemistry , Parabens/metabolism , Structure-Activity Relationship , Substrate Specificity
20.
Inorg Chem ; 59(4): 2288-2298, 2020 Feb 17.
Article in English | MEDLINE | ID: mdl-31986027

ABSTRACT

Cancer is the uncontrolled growth of abnormal cells via malignant cell division and rapid DNA replication. While DNA damaging molecules can cause cancer, their role as anticancer drugs are very significant. For this purpose, the novel series of paraben substituted spermine bridged(dispirobino) cyclotriphosphazene compounds 2-6 were synthesized for the first time, and their structures were characterized by various spectroscopic techniques. The solid-state structures and geometries of compounds 2-6 were determined using single-crystal X-ray structural analysis. In addition, it was confirmed by TGA that all compounds 1-6 showed high thermal stability. Two methods were used in order to investigate DNA interaction properties of the targeted molecules. While biosensor-based screening test that measures DNA hybridization efficiency on a biochip surface, the agarose gel electrophoresis method examines the effect of compounds on plasmid DNA structure. The results collected from the automated biosensor device and agarose gel electrophoresis have indicated that compounds 1, 5, and 6 showed higher DNA damage than the compounds 2-4. According to the biosensor results, compounds 1, 5, and 6 showed 85%, 69%, and 77% activity, respectively.


Subject(s)
DNA/chemistry , Organophosphorus Compounds/chemistry , Parabens/chemistry , Plasmids/chemistry , Spermine/analogs & derivatives , Biosensing Techniques , DNA Damage , Electrophoresis, Agar Gel , Organophosphorus Compounds/chemical synthesis , Parabens/chemical synthesis , Spermine/chemical synthesis
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