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Molecules (Basel, Switzerland) Jun 2022Natural or synthetic antioxidants with biomimetic fragments protect the functional and structural integrity of biological molecules at a minimum concentration, and may...
Natural or synthetic antioxidants with biomimetic fragments protect the functional and structural integrity of biological molecules at a minimum concentration, and may be used as potential chemotherapeutic agents. This paper is devoted to in silico and in vitro evaluation of the antioxidant and cytotoxic properties of synthetic analogues of natural compounds-aromatic oligosulfides. The antiradical and SOD-protective activity of oligosulfides was demonstrated in the reaction with O generated in enzymatic and non-enzymatic systems. It was found that phenol-containing disulfides significantly reduced the accumulation level of hydroperoxides and secondary carbonyl thiobarbituric acid reactive substances, which are primary products of oleic acid peroxidation. The antioxidant efficiency of bis(3,5-di--butyl-4-hydroxyphenyl) disulfide increased over time due to the synergistic action of the 2,6-di--butylphenol fragment and the disulfide linker. The highest cytotoxicity on the A-549 and HCT-116 cell lines was found for bis(3,4-dimethoxyphenyl) disulfide. Significant induction of apoptosis in HCT-116 cells in the presence of bis(3,4-dimethoxyphenyl) disulfide indicates the prospect of its use as an antitumor agent. The significant and moderate dependences revealed between various types of activities of the studied aromatic oligosulfides can be used in the development of a strategy for the synthesis and study of target-oriented compounds with predictable biological activity.
Topics: Antioxidants; Apoptosis; Disulfides; Phenol; Phenols
PubMed: 35745083
DOI: 10.3390/molecules27123961 -
Cellular and Molecular Life Sciences :... Mar 2010Phenolic lipids are a very diversified group of compounds derived from mono and dihydroxyphenols, i.e., phenol, catechol, resorcinol, and hydroquinone. Due to their... (Review)
Review
Phenolic lipids are a very diversified group of compounds derived from mono and dihydroxyphenols, i.e., phenol, catechol, resorcinol, and hydroquinone. Due to their strong amphiphilic character, these compounds can incorporate into erythrocytes and liposomal membranes. In this review, the antioxidant, antigenotoxic, and cytostatic activities of resorcinolic and other phenolic lipids are described. The ability of these compounds to inhibit bacterial, fungal, protozoan and parasite growth seems to depend on their interaction with proteins and/or on their membrane-disturbing properties.
Topics: Animals; Antimutagenic Agents; Antineoplastic Agents; Antioxidants; Humans; Lipids; Phenol
PubMed: 20213924
DOI: 10.1007/s00018-009-0193-1 -
International Journal of Molecular... Nov 2022Artificial gene delivery systems are in great demand from both scientific and practical biomedical points of view. In this paper, we present the synthesis of a new click...
Artificial gene delivery systems are in great demand from both scientific and practical biomedical points of view. In this paper, we present the synthesis of a new click chemistry calix[4]arene precursor with free lower rim and new water-soluble calixarene triazoles with 12 amino-groups on the upper rim (one with free phenol hydroxyl groups and two another containing four butyl or tetradecyl fragments). Aggregation in the series of amino-triazole calixarenes of different lipophilicity (calixarene with free phenol hydroxyl groups or butyl and tetradecyl fragments on the lower rim) was studied using dynamic light scattering and fluorescent pyrene probe. It was found that calix[4]arene with a free lower rim, like alkyl-substituted butyl calix[4]arene, forms stable submicron aggregates 150-200 nm in size, while the more lipophilic tetradecyl -substituted calix[4]arene forms micellar aggregates19 nm in size. Using UV-Vis spectroscopy, fluorimetry and CD, it was shown that amino-triazole calix[4]arenes bind to calf thymus DNA by classical intercalation. According to DLS and TEM data, all studied macrocycles cause significant DNA compaction, forming stable nanoparticles 50-20 nm in size. Among all studied calix[4]arenes the most lipophilic tetradecyl one proved to be the best for both binding and compaction of DNA.
Topics: Triazoles; Polyamines; Phenol; Calixarenes; DNA
PubMed: 36499212
DOI: 10.3390/ijms232314889 -
Clinical Nutrition (Edinburgh, Scotland) Nov 2022Berry (poly)phenol consumption has been associated with cardioprotective benefits, however little is known on the role the gut microbiome may play on such health... (Randomized Controlled Trial)
Randomized Controlled Trial
The effects of Aronia berry (poly)phenol supplementation on arterial function and the gut microbiome in middle aged men and women: Results from a randomized controlled trial.
BACKGROUND AND AIMS
Berry (poly)phenol consumption has been associated with cardioprotective benefits, however little is known on the role the gut microbiome may play on such health benefits. Our objective was to investigate the effects of aronia berry (poly)phenol consumption on cardiometabolic health and gut microbiome richness and composition in prehypertensive middle-aged men and women.
METHODS
A total of 102 prehypertensive participants were included in a parallel 12-week randomized double-blind placebo-controlled trial. Volunteers were randomly allocated to daily consume an encapsulated (poly)phenol-rich aronia berry extract (Aronia, n = 51) or a matched maltodextrin placebo (Control, n = 51). Blood pressure (BP) and arterial function (office and 24 h), endothelial function (measured as flow-mediated dilation), serum biochemistry (including blood lipids), plasma and urine (poly)phenol metabolites as well as gut microbiome composition through shotgun metagenomic sequencing were monitored over the study period. Relationships between vascular outcomes, (poly)phenol metabolites and gut microbiome were investigated using an integrated multi-levels approach.
RESULTS
A significant improvement in arterial indices measured as augmentation index (AIx) and pulse wave velocity (PWV) was found in the Aronia compared to Control group (awake Δ PWV = -0.24 m/s; 95% CI: -0.79, -0.01 m/s, P < 0.05; 24 h peripheral Δ AIx = -6.8; -11.2, -2.3, %, P = 0.003; 24 h central Δ AIx = -3.3; -5.5, -1.0, %, P = 0.006). No changes in BP, endothelial function or blood lipids were found following the intervention. Consumption of aronia (poly)phenols led to a significant increase in gut microbiome gene richness and in the abundance of butyrate-producing species such as Lawsonibacter asaccharolyticus and Intestinimonas butyriciproducens species, compared to Control group. Results from an approach including metabolomic, metagenomic and clinical outcomes highlighted associations between aronia-derived phenolic metabolites, arterial stiffness, and gut microbiome.
CONCLUSIONS
Aronia berry (poly)phenol consumption improved arterial function in prehypertensive middle-aged individuals, possibly via modulation of gut microbiome richness and composition based on the associations observed between these parameters.
CLINICAL TRIAL REGISTRY
The National Institutes of Health (NIH)-randomized trial records held on the NIH ClinicalTrials.gov website (NCT03434574). Aronia Berry Consumption on Blood Pressure.
Topics: Male; Middle Aged; Humans; Female; Photinia; Pulse Wave Analysis; Gastrointestinal Microbiome; Phenol; Blood Pressure; Phenols; Double-Blind Method; Dietary Supplements; Plant Extracts; Butyrates
PubMed: 36228567
DOI: 10.1016/j.clnu.2022.08.024 -
Nutrients Feb 2023The type 2 diabetes epidemic is real and hardly coming to an end in the upcoming years. The efforts of the scientific community to develop safer and more effective...
The type 2 diabetes epidemic is real and hardly coming to an end in the upcoming years. The efforts of the scientific community to develop safer and more effective compounds for type 2 diabetes based on the structure of natural (poly)phenols are remarkable and have indeed proven worthwhile after the introduction of gliflozins in clinical practice. However, low-quality reports on the antidiabetic potential of plant-derived lipophilic (poly)phenols continue to pile up in the literature. Many of these compounds continue to be published as promising functional nutrients and antidiabetic pharmaceutical leads without consideration of their Pan-Assay Interference Compounds (PAINS) profile. This evidence-based opinion article conveys the authors' perspectives on the natural (poly)phenol artillery as a valuable and reliable source of bioactive compounds for diabetes. Ultimately, in light of the already established membrane-perturbing behavior of lipophilic (poly)phenols, together with the multiple benefits that may come with the introduction of a -glucosyl moiety in bioactive compounds, we aim to raise awareness of the importance of contemplating the shift to (poly)phenol-carbohydrate combinations in the development of functional nutrients, as well as in the early stages of antidiabetic drug discovery.
Topics: Humans; Diabetes Mellitus, Type 2; Phenol; Phenols; Hypoglycemic Agents; Carbohydrates
PubMed: 36839354
DOI: 10.3390/nu15040996 -
Environment International Dec 2022Non-persistent endocrine-disrupting chemicals (EDCs), including phthalates and phenols, are ubiquitous in both the environment and human body. A growing body of... (Review)
Review
Non-persistent endocrine-disrupting chemicals (EDCs), including phthalates and phenols, are ubiquitous in both the environment and human body. A growing body of epidemiologic studies have identified concerning links between EDCs and adverse reproductive and developmental health effects. Despite consistent evidence, risk assessments and policy interventions often arrive late. This presents an urgent need to identify evidence-based interventions for implementation at both clinical and community levels to reduce EDC exposure, especially in susceptible populations. The reproductive life cycle (menarche to menopause for females and after pubertal onset for males) includes some of the most vulnerable periods to environmental exposures, such as the preconception and perinatal stages, representing a key window of opportunity to intervene and prevent unfavorable health outcomes. This review aims to synthesize and assess behavioral, dietary, and residential EDC-driven interventions to develop recommendations for subsequent, larger-scale studies that address knowledge-gaps in current interventions during the reproductive life cycle. We selected 21 primary interventions for evaluation, in addition to four supplemental interventions. Among these, accessible (web-based) educational resources, targeted replacement of (known) toxic products, and personalization of the intervention through meetings and support groups, were the most promising strategies for reducing EDC concentrations. However, we document a paucity of interventions to prevent phthalate and phenol exposures during the reproductive years, especially among men. Accordingly, we recommend additional, larger clinical and community-based intervention studies to reduce EDC exposure. Specifically, future intervention studies should focus on short-term, mid-, and long-term exposure reduction to phthalates and phenols. The latter, especially, is required for the development of clinical and public health guidelines to promote reproductive and developmental health globally.
Topics: Humans; Phenol
PubMed: 36283156
DOI: 10.1016/j.envint.2022.107576 -
Organic Letters Jun 2023A C-N bond-forming cross-dehydrogenative coupling of a collection of Tyr-containing peptides and estrogens with heteroarenes is described. This oxidative coupling is...
A C-N bond-forming cross-dehydrogenative coupling of a collection of Tyr-containing peptides and estrogens with heteroarenes is described. This oxidative coupling is distinguished by its scalability, operational simplicity, and air tolerance and enables the appendance of phenothiazines and phenoxazines in phenol-like compounds. When incorporated into a Tb(III) metallopeptide, the Tyr-phenothiazine moiety acts as a sensitizer for the Tb(III) ion, providing a new tool for the design of luminescent probes.
Topics: Amination; Phenol; Oxidative Coupling; Phenols
PubMed: 37284781
DOI: 10.1021/acs.orglett.3c01560 -
International Journal of Molecular... Aug 2022The π-π interaction is a major driving force that stabilizes protein assemblies during protein folding. Recent studies have additionally demonstrated its involvement...
The π-π interaction is a major driving force that stabilizes protein assemblies during protein folding. Recent studies have additionally demonstrated its involvement in the liquid-liquid phase separation (LLPS) of intrinsically disordered proteins (IDPs). As the participating residues in IDPs are exposed to water, π-π interactions for LLPS must be modeled in water, as opposed to the interactions that are often established at the hydrophobic domains of folded proteins. Thus, we investigated the association of free energies of benzene and phenol dimers in water by integrating van der Waals (vdW)-corrected density functional theory (DFT) and DFT in classical explicit solvents (DFT-CES). By comparing the vdW-corrected DFT and DFT-CES results with high-level wavefunction calculations and experimental solvation free energies, respectively, we established the quantitative credibility of these approaches, enabling a reliable prediction of the benzene and phenol dimer association free energies in water. We discovered that solvation influences dimer association free energies, but not significantly when no direct hydrogen-bond-type interaction exists between two monomeric units, which can be explained by the enthalpy-entropy compensation. Our comprehensive computational study of the solvation effect on π-π interactions in water could help us understand the molecular-level driving mechanism underlying the IDP phase behaviors.
Topics: Benzene; Intrinsically Disordered Proteins; Phenol; Thermodynamics; Water
PubMed: 36077201
DOI: 10.3390/ijms23179811 -
IARC Monographs on the Evaluation of... 1999
Review
Topics: Animals; Carcinogenicity Tests; Carcinogens; Humans; Mutagenicity Tests; Mutagens; Neoplasms; Neoplasms, Experimental; Occupational Exposure; Phenol
PubMed: 10476471
DOI: No ID Found -
IARC Monographs on the Evaluation of... 1989
Review
Topics: Animals; Carcinogens; Chemical Phenomena; Chemistry; Humans; Phenol; Phenols; Risk Factors
PubMed: 2699901
DOI: No ID Found