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Molecules (Basel, Switzerland) May 2017Hydroxybenzylidene hydrazines exhibit a wide spectrum of biological activities. Here, we report synthesis and free radical scavenging activity of nine new...
Hydroxybenzylidene hydrazines exhibit a wide spectrum of biological activities. Here, we report synthesis and free radical scavenging activity of nine new N-(hydroxybenzylidene)-N'-[2,6-dinitro-4-(trifluoromethyl)]phenylhydrazines. The chemical structures of these compounds were confirmed by 1H-NMR, 13C-NMR, 19F-NMR, IR spectroscopy, LC-MS, and elemental analysis. The prepared compounds were tested for their activity to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH), galvinoxyl radical (GOR), and 2,2'-azino-bis(3-ethylbenzothiazoline)-6-sulphonic acid (ABTS) radicals. The free radical scavenging activity expressed as SC50 values of these compounds varied in a wide range, from a strong to no radical scavenging effect. The most effective radical scavengers were hydroxybenzylidene hydrazines containing three hydroxyl groups in the benzylidene part of their molecules. The prepared compounds were also tested for their activity to inhibit photosynthetic electron transport in spinach chloroplasts. IC50 values of these compounds varied in wide range, from an intermediate to no inhibitory effect.
Topics: Biphenyl Compounds; Free Radical Scavengers; Hydrazines; Picrates; Proton Magnetic Resonance Spectroscopy
PubMed: 28555047
DOI: 10.3390/molecules22060894 -
International Journal of Nanomedicine 2023Honokiol (HNK) is a small-molecule polyphenol that has garnered considerable attention due to its diverse pharmacological properties, including antitumor,... (Review)
Review
Honokiol (HNK) is a small-molecule polyphenol that has garnered considerable attention due to its diverse pharmacological properties, including antitumor, anti-inflammatory, anti-bacterial, and anti-obesity effects. However, its clinical application is restricted by challenges such as low solubility, poor bioavailability, and rapid metabolism. To overcome these limitations, researchers have developed a variety of nano-formulations for HNK delivery. These nano-formulations offer advantages such as enhanced solubility, improved bioavailability, extended circulation time, and targeted drug delivery. However, existing reviews of HNK primarily focus on its clinical and pharmacological features, leaving a gap in the comprehensive evaluation of HNK delivery systems based on nanotechnology. This paper aims to bridge this gap by comprehensively reviewing different types of nanomaterials used for HNK delivery over the past 15 years. These materials encompass vesicle delivery systems, nanoparticles, polymer micelles, nanogels, and various other nanocarriers. The paper details various HNK nano-delivery strategies and summarizes their latest applications, development prospects, and future challenges. To compile this review, we conducted an extensive search using keywords such as "honokiol", "nanotechnology", and "drug delivery system" on reputable databases, including PubMed, Scopus, and Web of Science, covering the period from 2008 to 2023. Through this search, we identified and selected approximately 90 articles that met our specific criteria.
Topics: Drug Delivery Systems; Biphenyl Compounds; Micelles; Nanotechnology; Nanoparticles; Lignans
PubMed: 38026538
DOI: 10.2147/IJN.S431409 -
Current Topics in Medicinal Chemistry 2017This study evaluated the antioxidative effects of magnolol based on the mouse model induced by Enterotoxigenic Escherichia coli (E. coli, ETEC). All experimental mice... (Review)
Review
This study evaluated the antioxidative effects of magnolol based on the mouse model induced by Enterotoxigenic Escherichia coli (E. coli, ETEC). All experimental mice were equally treated with ETEC suspensions (3.45×109 CFU/ml) after oral administration of magnolol for 7 days at the dose of 0, 100, 300 and 500 mg/kg Body Weight (BW), respectively. The oxidative metabolites and antioxidases for each sample (organism of mouse) were determined: Malondialdehyde (MDA), Nitric Oxide (NO), Glutathione (GSH), Myeloperoxidase (MPO), Catalase (CAT), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GPx). In addition, we also determined the corresponding mRNA expressions of CAT, SOD and GPx as well as the Total Antioxidant Capacity (T-AOC). The experiment was completed with a theoretical study that predicts a series of 79 ChEMBL activities of magnolol with 47 proteins in 18 organisms using a Quantitative Structure- Activity Relationship (QSAR) classifier based on the Moving Averages (MAs) of Rcpi descriptors in three types of experimental conditions (biological activity with specific units, protein target and organisms). Six Machine Learning methods from Weka software were tested and the best QSAR classification model was provided by Random Forest with True Positive Rate (TPR) of 0.701 and Area under Receiver Operating Characteristic (AUROC) of 0.790 (test subset, 10-fold crossvalidation). The model is predicting if the new ChEMBL activities are greater or lower than the average values for the magnolol targets in different organisms.
Topics: Animals; Biphenyl Compounds; Enteritis; Enterotoxigenic Escherichia coli; Escherichia coli Infections; Lignans; Machine Learning; Mice; Oxidative Stress
PubMed: 28828993
DOI: 10.2174/1568026617666170821130315 -
Chemical & Pharmaceutical Bulletin 2023Palladium-catalyzed, hydroxy-group-directed C-H arylation of [1,1'-biphenyl]-2-ols with chloroarenes was performed. The reaction showed a broad substrate scope and was...
Palladium-catalyzed, hydroxy-group-directed C-H arylation of [1,1'-biphenyl]-2-ols with chloroarenes was performed. The reaction showed a broad substrate scope and was successfully applied to pharmaceuticals containing a chloro group. Using 2-heteroarylphenols instead of [1,1'-biphenyl]-2-ols also yielded the desired products. The arylated product was further transformed into a triphenylene derivative.
Topics: Molecular Structure; Palladium; Catalysis; Biphenyl Compounds
PubMed: 36724980
DOI: 10.1248/cpb.c22-00809 -
The Journal of General and Applied... Feb 2003Many members of the sphingomonad genus isolated from different geological areas can degrade a wide variety of polycyclic aromatic hydrocarbons (PAHs) and related... (Comparative Study)
Comparative Study Review
Many members of the sphingomonad genus isolated from different geological areas can degrade a wide variety of polycyclic aromatic hydrocarbons (PAHs) and related compounds. These sphingomonads such as Sphingobium yanoikuyae strain B1, Novosphingobium aromaticivorans strain F199, and Sphingobium sp. strain P2 have been found to possess a unique group of genes for aromatic degradation, which are distantly related with those in pseudomonads and other genera reported so far both in sequence homology and gene organization. Genes for aromatics degradation in these sphingomonads are complexly arranged; the genes necessary for one degradation pathway are scattered through several clusters. These aromatic catabolic gene clusters seem to be conserved among many other sphingomonads such as Sphingobium yanoikuyae strain Q1, Sphingomonas paucimobilis strain TNE12, S. paucimobilis strain EPA505, Sphingobium agrestis strain HV3, and Sphingomonas chungbukensis strain DJ77. Furthermore, some genes for naphthalenesulfonate degradation found in Sphingomonas xenophaga strain BN6 also share a high sequence homology with their homologues found in these sphingomonads. On the other hand, protocatechuic catabolic gene clusters found in fluorene-degrading Sphingomonas sp. strain LB126 appear to be more closely related with those previously found in lignin-degrading S. paucimobilis SYK-6 than the genes in this group of sphingomonads. This review summarizes the information on the distribution of these strains and relationships among their aromatic catabolic genes.
Topics: Alphaproteobacteria; Biodegradation, Environmental; Biological Evolution; Biphenyl Compounds; DNA, Bacterial; Fluorenes; Genes, Bacterial; Models, Genetic; Molecular Structure; Phylogeny; Polycyclic Aromatic Hydrocarbons; Soil Microbiology
PubMed: 12682862
DOI: 10.2323/jgam.49.1 -
CNS Drug Reviews 2005Glutamate is the major excitatory transmitter in the brain. Recent developments in the molecular biology and pharmacology of the... (Review)
Review
Glutamate is the major excitatory transmitter in the brain. Recent developments in the molecular biology and pharmacology of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-subtype of glutamate receptors have led to the discovery of selective, potent and systemically active AMPA receptor potentiators. These molecules enhance synaptic transmission and play important roles in plasticity and cognitive processes. In the present studies we characterized a novel AMPA receptor potentiator, LY503430, on recombinant human GLU(A1-4) and native preparations in vitro, and then evaluated the potential neuroprotective effects of the molecule in rodent models of Parkinson's disease. Results indicated that at submicromolar concentrations LY503430 selectively enhanced glutamate-induced calcium influx into HEK293 cells transfected with human GLU(A1), GLU(A2), GLU(A3), or GLU(A4) AMPA receptors. The molecule also potentiated AMPA-mediated responses in native cortical, hippocampal and substantia nigra neurones. LY503430 had good oral bioavailability in both rats and dogs. We also report here that LY503430 provided dose-dependent functional and histological protection in animal models of Parkinson's disease. The neurotoxicity following unilateral infusion of 6-hyrdoxydopamine (6-OHDA) into either the substantia nigra or the striatum of rats and that following systemic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice were reduced. Interestingly, LY503430 also had neurotrophic actions on functional and histological outcomes when treatment was delayed until well after (6 or 14 days) the lesion was established. LY503430 also produced some increase in brain derived neurotrophic factor (BDNF) in the substantia nigra and a dose-dependent increase in growth associated protein-43 (GAP-43) expression in the striatum. Therefore, we propose that AMPA receptor potentiators such as LY503430 offer the potential of a new disease modifying therapy for Parkinson's disease.
Topics: Amides; Animals; Behavior, Animal; Biphenyl Compounds; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Drug Interactions; Growth Substances; Humans; In Vitro Techniques; Neurites; Neurons; Parkinson Disease; Prefrontal Cortex; Rats; Receptors, Glutamate; Rodentia
PubMed: 15867954
DOI: 10.1111/j.1527-3458.2005.tb00037.x -
PloS One 2018The hepatocellular carcinoma is one of the most common malignant tumour with high level of mortality rate due to its rapid progression and high resistance to...
The hepatocellular carcinoma is one of the most common malignant tumour with high level of mortality rate due to its rapid progression and high resistance to conventional chemotherapies. Thus, the search for novel therapeutic leads is of global interest. Herein, a small set of derivatives of magnolol 1 and honokiol 2, the main components of Magnolia grandiflora and Magnolia obovata, were evaluated in in vitro assay using tumoral hepatocytes. The pro-drug approach was applied as versatile strategy to the improve bioactivity of the compounds by careful transformation of the hydroxyl groups of magnolol 1 and honokiol 2 in suitable ester derivatives. Compounds 10 and 11 resulted to be more potent than the parental honokiol 2 at concentration down to 1 μM with complete viability of treated fibroblast cells up to concentrations of 80 μM. The combination of a butyrate ester and a bare phenol-OH group in the honokiol structure seemed to play a significant role in the antiproliferative activity identifying an interesting pharmacological clue against hepatocellular carcinoma.
Topics: Biphenyl Compounds; Carbon-13 Magnetic Resonance Spectroscopy; Carcinoma, Hepatocellular; Cell Line; Cell Line, Tumor; Drug Screening Assays, Antitumor; Humans; Lignans; Liver Neoplasms; Proton Magnetic Resonance Spectroscopy
PubMed: 29415009
DOI: 10.1371/journal.pone.0192178 -
Environment International Nov 20104-Monochlorobiphenyl (PCB3) is readily converted by xenobiotic-metabolizing enzymes to dihydroxy-metabolites and quinones. The PCB3 hydroquinone (PCB3-HQ;...
4-Monochlorobiphenyl (PCB3) is readily converted by xenobiotic-metabolizing enzymes to dihydroxy-metabolites and quinones. The PCB3 hydroquinone (PCB3-HQ; 2-(4'-chlorophenyl)-1,4-hydroquinone) induces chromosome loss in Chinese Hamster V79 cells, whereas the para-quinone (PCB3-pQ; 2-(4'-chlorophenyl)-1,4-benzoquinone) very efficiently induces gene mutations and chromosome breaks. Apparently, each of these two metabolites, which are a redox pair, has a different spectrum of genotoxic effects due to different, metabolite-specific mechanisms. We hypothesized that the HQ requires enzymatic activation by peroxidases with the formation of reactive oxygen species (ROS) as the ultimate genotoxin, whereas the pQ reacts directly with nucleophilic sites in DNA and/or proteins. To examine this hypothesis, we employed two cell lines with different myeloperoxidase (MPO) activities, MPO-rich HL-60 and MPO-deficient Jurkat cells, and measured cytotoxicity, DNA damage (COMET assay), MPO activity, intracellular levels of reactive oxygen species (ROS) and intracellular free -SH groups (monochlorobimane assay, MCB) and free GSH contents (enzyme recycling method) after treatment with PCB3-HQ and PCB3-pQ. We also examined the modulation of these effects by normal/low temperature, pre-treatment with an MPO inhibitor (succinylacetone, SA), or GSH depletion. PCB3-p-Q increased intracellular ROS levels and induced DNA damage in both HL-60 and Jurkat cells at 37°C and 6°C, indicating a direct, MPO-independent mode of activity. It also strongly reduced intracellular free -SH groups and GSH levels in normal and GSH-depleted cells. Thus the ROS increase could be caused by reduced protection by GSH or non-enzymatic autoxidation of the resulting PCB3-HQ-GSH adduct. PCB3-HQ did not produce a significant reduction of intracellular GSH in HL-60 cells and reduced intracellular free -SH groups only at the highest concentration tested in GSH depleted cells. Moreover, PCB3-HQ induced DNA damage and ROS production only at 37 °C in HL-60 cells, not at 6 °C or in Jurkat cells at either temperature; no significant DNA damage and ROS production was observed in HL-60 cells at 37 °C if MPO activity was inhibited by SA. These studies show that the effects of PCB3-HQ are enzyme dependent, i.e. PCB3-HQ is oxidized by MPO in HL-60 cells with the generation of ROS and induction of DNA damage. However, this is not the case with the PCB3-pQ, which may produce DNA damage by the reactivity of the quinone with the DNA or nuclear proteins, or possibly by indirectly increasing intracellular ROS levels by GSH depletion. These different modes of action explain not only the different types of genotoxicity observed previously, but also suggest different organ specificity of these genotoxins.
Topics: Biphenyl Compounds; Cell Line; Comet Assay; DNA Damage; Humans; Mutagens; Peroxidase; Reactive Oxygen Species; Sulfhydryl Compounds; Temperature
PubMed: 20129669
DOI: 10.1016/j.envint.2009.12.004 -
The Biochemical Journal Jan 1979Cunninghamella elegans grown on Sabouraud dextrose broth transformed biphenyl to produce 2-, 3- and 4-hydroxybiphenyl, as well as 4,4'-dihydroxybiphenyl as free phenols....
Cunninghamella elegans grown on Sabouraud dextrose broth transformed biphenyl to produce 2-, 3- and 4-hydroxybiphenyl, as well as 4,4'-dihydroxybiphenyl as free phenols. A compound tentatively identified as 2,4'-dihydroxybiphenyl was also produced. When 4-hydroxybiphenyl or 2-hydroxybiphenyl replaced biphenyl as the substrate, C. elegans produced 4,4'-dihydroxybiphenyl and 2,5-dihydroxybiphenyl respectively. The compound identified as 2,4'-dihydroxybiphenyl was produced from both substrates. A survey of 11 species of fungi known to degrade hydrocarbons revealed two species that were comparable to C. elegans in their ability to convert biphenyl into free phenols. In addition to free phenolic metabolites, deconjugation experiments indicated that 44% of the known metabolites present in the culture filtrate were present in the form of conjugates. These results suggest that the transformation of biphenyl by C. elegans is similar to that found in mammalian systems.
Topics: Biphenyl Compounds; Kinetics; Models, Biological; Mucorales; Phenols
PubMed: 435280
DOI: 10.1042/bj1780223 -
International Journal of Molecular... Dec 2016The peroxisome proliferator-activated receptor γ (PPARγ) ligands are important therapeutic drugs for the treatment of type 2 diabetes, obesity and cardiovascular...
The peroxisome proliferator-activated receptor γ (PPARγ) ligands are important therapeutic drugs for the treatment of type 2 diabetes, obesity and cardiovascular diseases. In particular, partial agonists and non-agonists are interesting targets to reduce glucose levels, presenting few side effects in comparison to full agonists. In this work, we present a set of CHARMM-based parameters of a molecular mechanics force field for two PPARγ ligands, GQ16 and SR1664. GQ16 belongs to the thiazolidinedione class of drugs and it is a PPARγ partial agonist that has been shown to promote the "browning" of white adipose tissue. SR1664 is the precursor of the PPARγ non-agonist class of ligands that activates PPARγ in a non-classical manner. Here, we use quantum chemical calculations consistent with the CHARMM protocol to obtain bonded and non-bonded parameters, including partial atomic charges and effective torsion potentials for both molecules. The newly parameterized models were evaluated by examining the behavior of GQ16 and SR1664 free in water and bound to the ligand binding pocket of PPARγ using molecular dynamics simulations. The potential parameters derived here are readily transferable to a variety of pharmaceutical compounds and similar PPARγ ligands.
Topics: Algorithms; Binding Sites; Biphenyl Compounds; Ligands; Molecular Docking Simulation; PPAR gamma; Protein Binding; Thiazolidinediones
PubMed: 28025495
DOI: 10.3390/ijms18010015