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Expert Opinion on Therapeutic Patents Dec 2023Schiff bases are compounds with characteristic features of azomethine linkage (-C=N-). Schiff bases are capable of coordinating with metal ions via azomethine nitrogen.... (Review)
Review
INTRODUCTION
Schiff bases are compounds with characteristic features of azomethine linkage (-C=N-). Schiff bases are capable of coordinating with metal ions via azomethine nitrogen. Schiff base derivatives and their metal complexes are known for intriguing novel therapeutic properties. In organic synthesis, the Schiff base reaction is prime in creating the C-N bond. Synthetic accessibility and structural diversity are the salient features for facile synthesis of Schiff base hybrids via a condensation reaction between an aldehyde/ketone and primary amines.
AREA COVERED
This review aims to provide a comprehensive overview of the commendable medicinal applications of Schiff base derivatives and their metal complexes patented from 2016 to 2023.
EXPERT OPINION
Schiff base derivatives are exceptional molecules for their assorted applications in medicinal chemistry. Several Schiff base products are marketed as drugs, and plenty of room is available for the purposive synthesis of new compounds in a diverse pool of disciplines. Expansion in the derivatization of Schiff bases in innumerable directions with multitudinous applications makes them 'magical molecules.' These compounds have proved extraordinary, from medicinal chemistry to other fields outside medicine. This review covers the therapeutic importance of Schiff base derivatives and aims to cover the patents published in recent years (2016-2023).
Topics: Humans; Coordination Complexes; Chemistry, Pharmaceutical; Schiff Bases; Patents as Topic; Ligands; Azo Compounds; Thiosemicarbazones
PubMed: 38115554
DOI: 10.1080/13543776.2023.2297729 -
Phytomedicine : International Journal... Mar 2024Osthole is active constituent of Cnidium monnieri (L.) Cuss. with various physiological functions including anti-inflammation and anti-lipedemic effects. However, the...
BACKGROUND
Osthole is active constituent of Cnidium monnieri (L.) Cuss. with various physiological functions including anti-inflammation and anti-lipedemic effects. However, the regulatory activity of osthole in colorectal cancer development, focusing on mitochondrial metabolism, is not well known.
HYPOTHESIS/PURPOSE
We hypothesized that osthole may suppress progression of colorectal cancer and aimed to determine the underlying mitochondrial metabolism and the autophagic flux.
STUDY DESIGN
In this study, we elucidated the mechanism of action of osthole in colorectal cancer using an in vivo azoxymethane/dextran sodium sulfate (AOM/DSS) mouse model and an in vitro cell culture system.
METHODS
AOM/DSS mouse model was established and analyzed the effects of osthole on survival rate, diseases activity index, number of tumor and histopathology. Then, cell based assays including viability, cell cycle, reactive oxygen species (ROS), apoptosis, calcium efflux, and mitochondrial function were analyzed. Moreover, osthole-mediated signaling was demonstrated by western blot analyses.
RESULTS
Osthole effectively suppressed the growth of colorectal tumors and alleviated AOM/DSS-induced intestinal injury. Osthole restored the function of goblet cells and impaired the expression of Claudin1 and Axin1 impaired by AOM/DSS. In addition, osthole specifically showed cytotoxicity in colorectal carcinoma cells, but not in normal colon cells. Osthole decreased the ASC/caspase-1/IL-1β inflammasome pathway and induced mitochondrial dysfunction in redox homeostasis, calcium homeostasis. Furthermore, osthole inhibited both oxidative phosphorylation (OXPHOS) and glycolysis, leading to the suppression of ATP production. Moreover, via combination treatment with chloroquine (CQ), we demonstrated that osthole impaired autophagic flux, leading to apoptosis of HCT116 and HT29 cells. Finally, we elucidated that the functional role of tiRNA regulated by osthole directly affects the cellular fate of colon cancer cells.
CONCLUSION
These results suggest that osthole has the potential to manage progression of colorectal cancer by regulating autophagy- and mitochondria-mediated signal transduction.
Topics: Mice; Animals; Calcium; Mitochondria; Colorectal Neoplasms; Azoxymethane; Autophagy; Dextran Sulfate; Coumarins
PubMed: 38295666
DOI: 10.1016/j.phymed.2024.155383 -
Scientific Reports Sep 2023This study aimed to evaluate the influence of CO and temperature on glyphosate-resistant and susceptible biotypes of Amaranthus palmeri (Palmer amaranth) in terms of...
This study aimed to evaluate the influence of CO and temperature on glyphosate-resistant and susceptible biotypes of Amaranthus palmeri (Palmer amaranth) in terms of morphological development. Height (cm), stem diameter (cm), leaf area (cm), number of leaves, leaf, stem, and root dry matter, plant volume (m), as well as shoot-to-root allometry were evaluated. The Palmer amaranth biotypes were grown under four different scenarios: 1-low temperature (23/33 °C) and CO (410 ± 25 ppm); 2-low temperature (23/33 °C) and high CO (750 ± 25 ppm); 3-high temperature (26/36 °C) and low CO (410 ± 25 ppm); and 4-high temperature (26/36 °C) and CO (750 ± 25 ppm). Between CO and temperature, the majority of differences observed were driven by CO levels. Palmer amaranth grown under 750 ppm of CO was 15.5% taller, displayed 10% more leaf area (cm), 18% more stem dry matter, and had a 28.4% increase in volume (m) compared to 410 ppm of CO. GA2017 and GA2020 were 18% and 15.5% shorter, respectively. The number of leaves was 27% greater for GA2005. Plant volume decreased in GA2017 (35.6%) and GA2020 (23.8%). The shoot-to-root ratio was isomeric, except at 14 and 21 DAT, where an allometric growth towards shoot development was significant. Palmer amaranth biotypes responded differently to elevated CO, and the impacts of temperature need further investigation on weed physiology. Thus, environmental and genetic background may affect the response of glyphosate-resistant and susceptible populations to climate change scenarios.
Topics: Amaranth Dye; Amaranthus; Carbon Dioxide; Regeneration; Temperature; Glyphosate
PubMed: 37660074
DOI: 10.1038/s41598-023-41121-5 -
Advanced Healthcare Materials Mar 2024Despite the intense progress of photodynamic and chemotherapy, however, they cannot prevent solid tumor invasion, metastasis, and relapse, along with inferior efficacy...
Despite the intense progress of photodynamic and chemotherapy, however, they cannot prevent solid tumor invasion, metastasis, and relapse, along with inferior efficacy and severe side effects. The hypoxia-responsive nanoprodrugs integrating photodynamic functions are highly sought to address the above-mentioned problems and overcome the tumor hypoxia-reduced efficacy. Herein, a hypoxia-responsive tetrameric supramolecular polypeptide nanoprodrug (SPN-TAPP-PCB4) is constructed from the self-assembly of tetrameric porphyrin-central poly(l-lysine-azobenzene-chlorambucil) (TAPP-(PLL-Azo-CB)4) and an anionic water-soluble [2]biphenyl-extended-pillar[6]arene (AWBpP6) via the synergy of hydrophobic, π-π stacking, and host-guest interactions. Upon laser irradiation, the central TAPP can convert oxygen to generate single oxygen ( O ) to kill tumor cells. Furthermore, under the acidic and PDT-aggravated hypoxia tumor cell microenvironment, SPN-TAPP-PCB4 is rapidly disassembled, and then efficiently releases activated CB through the hypoxic-responsive cleavage of azobenzene linkages. Both in vitro and in vivo biological studies showcase synergistic cancer-killing actions between photodynamic therapy (PDT) and chemotherapy (CT) with negligible toxicity. Consequently, this supramolecular polypeptide nanoprodrug offers an effective strategy to design a hypoxia-responsive nanoprodrug for a potential combo PDT-CT transition.
Topics: Humans; Hypoxia; Oxygen; Azo Compounds; Peptides
PubMed: 37924332
DOI: 10.1002/adhm.202303308 -
Cancer Research Feb 2024A promising approach to treat solid tumors involves disrupting their reliance on glutamine, a key component for various metabolic processes. Traditional attempts using...
A promising approach to treat solid tumors involves disrupting their reliance on glutamine, a key component for various metabolic processes. Traditional attempts using glutamine inhibitors like 6-diazo-5-oxo-L-norleucine (DON) and CB-839 were unsuccessful, but new hope arises with DRP-104, a prodrug of DON. This compound effectively targets tumor metabolism while minimizing side effects. In a recent study published in Nature Cancer, Encarnación-Rosado and colleagues demonstrated in preclinical models that pancreatic ductal adenocarcinoma (PDAC) responds well to DRP-104, although tumors adapt through the MEK/ERK signaling pathway, which can be countered by the MEK inhibitor trametinib. In a related study, Recouvreux and colleagues found that DON is effective against pancreatic tumors, revealing that PDAC tumors upregulate asparagine synthesis in response to DON, making them susceptible to asparaginase treatment. Both studies underscore the potential of inhibiting glutamine metabolism and adaptive pathways as a promising strategy against PDAC. These findings pave the way for upcoming clinical trials utilizing DRP-104 and similar glutamine antagonists in the battle against solid tumors.
Topics: Humans; Glutamine; Diazooxonorleucine; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Enzyme Inhibitors; Mitogen-Activated Protein Kinase Kinases
PubMed: 38117482
DOI: 10.1158/0008-5472.CAN-23-3954 -
Pakistan Journal of Pharmaceutical... Jan 2024Hydrazones 1-6, azo-pyrazoles 7-9 and azo-pyrimidines 10-15 are compounds that exhibit antibacterial activity. The mode of action and structures of these derivatives...
Hydrazones 1-6, azo-pyrazoles 7-9 and azo-pyrimidines 10-15 are compounds that exhibit antibacterial activity. The mode of action and structures of these derivatives have been previously confirmed as antibacterial. In this investigation, biological screening and molecular docking studies were performed for derivatives 1-15, with compounds 2, 7, 8, 14 and 15 yielding the best energy scores (from -20.7986 to -10.5302 kcal/mol). Drug-likeness and in silico ADME prediction for the most potent derivatives, 2, 7, 8, 14 and 15, were predicted (from 84.46 to 96.85%). The latter compounds showed good recorded physicochemical properties and pharmacokinetics. Compound 8 demonstrated the strongest inhibition, which was similar to the positive control (eflornithine) against Trypanosoma brucei brucei (WT), with an EC of 25.12 and 22.52µM, respectively. Moreover, compound 14 exhibited the best activity against Leishmania mexicana promastigotes and Leishmania major promastigotes (EC =46.85; 40.78µM, respectively).
Topics: Pyrimidines; Molecular Docking Simulation; Trypanosoma brucei brucei; Pyrazoles; Trypanocidal Agents; Leishmania mexicana; Leishmania major; Antiprotozoal Agents; Computer Simulation; Azo Compounds; Structure-Activity Relationship; Parasitic Sensitivity Tests
PubMed: 38747267
DOI: No ID Found -
Pest Management Science Dec 2023Agricultural pests have caused huge losses in agricultural production and threaten global food security. Synthetic insecticides remain the major control method. However,...
BACKGROUND
Agricultural pests have caused huge losses in agricultural production and threaten global food security. Synthetic insecticides remain the major control method. However, with the rapid development of pest resistance and the increasingly stringent regulations on pesticide usage, the development of efficient insecticides with novel structures is particularly urgent.
RESULTS
Twenty-six novel anthranilic diamide derivatives containing the thiazole moiety were designed based on the scaffold hopping strategy. Bioassay results indicated that compound 6e exhibited excellent insecticidal activity against a susceptible strain of diamondback moth (Plutella xylostella) with a median lethal concentration (LC ) of 0.65 mg L , which was similar to chlorantraniliprole (LC = 0.53 mg L ). Compound 6e showed marginally lower (LC = 50.45 mg L ) insecticidal activity than chlorantraniliprole (LC = 31.98 mg L ) on chlorantraniliprole-resistant P. xylostella larvae, suggesting a cross-resistance of compound 6e with chlorantraniliprole (resistance ratios, 77.6-fold and 60.3-fold, respectively). Compound 6e also showed good insecticidal activity against fall armyworm and beet armyworm with pest mortalities of 74% and 64%, respectively, at 5 mg L concentration. In addition, compounds 6e and 12a showed delayed toxicity against red imported fire ant with mortality rates of 84% and 85% (respectively) after 5 days of treatment at 1.0 mg L , which were superior to that of chlorantraniliprole.
CONCLUSION
The introduction of thiazole into anthranilic diamide scaffolds resulted in insecticidal leads 6e and 12a with excellent insecticidal activities and potential application in controlling red imported fire ants. The work also guides the discovery of insecticidal molecules with thiazole-containing anthranilic diamide scaffold. © 2023 Society of Chemical Industry.
Topics: Animals; Insecticides; Structure-Activity Relationship; Diamide; Larva; Moths; Thiazoles
PubMed: 37599274
DOI: 10.1002/ps.7734 -
Colloids and Surfaces. B, Biointerfaces Nov 2023Azo dye methyl orange (MO) and shell rotting cause great environmental pollution. Most of the common dye adsorbents are difficult to produce, not environmentally...
Azo dye methyl orange (MO) and shell rotting cause great environmental pollution. Most of the common dye adsorbents are difficult to produce, not environmentally friendly and it is always difficult to utilize the shell resources effectively. In this study, shell-based economical and environmentally friendly magnetic hydroxyapatite microsphere adsorbents (FeO @SiO/HAP) were developed for the removal of MO from simulated wastewater by sol-gel and hydrothermal synthesis methods. The effects of solution pH, initial concentration, adsorption time and system temperature on the adsorption effect were investigated, and the repeat recovery performance was explored. The equilibrium adsorption data follow the Freundlich isotherm and pseudo-second-order kinetic curves, and the analysis indicates that the adsorption process is spontaneously exothermic. The adsorption capacities of MO were up to 94.48% and 88.94%, under the acidic environment of pH = 4, respectively, and had good recycling performance. The results provide a high-value utilization pathway for waste shell resources and focus on the removal of azo dyes. This is expected to provide new development ideas for the environmental hazards caused by acid dye wastewater discharged into rivers and oceans, as well as the problems of soil pollution and resource waste caused by weathering and corrosion of shells.
Topics: Adsorption; Wastewater; Durapatite; Microspheres; Silicon Dioxide; Azo Compounds; Kinetics; Magnetic Phenomena; Water Pollutants, Chemical; Hydrogen-Ion Concentration
PubMed: 37738869
DOI: 10.1016/j.colsurfb.2023.113561 -
Journal of Colloid and Interface Science Aug 2024In this study, nitrogen-doped carbon dots (N-CDs) were facilely fabricated by one-pot hydrothermal method with levulinic acid and triethanolamine. A fluorescent sensor...
In this study, nitrogen-doped carbon dots (N-CDs) were facilely fabricated by one-pot hydrothermal method with levulinic acid and triethanolamine. A fluorescent sensor array was established for identifying azo compounds including Sudan Orange G (SOG), p-diaminoazobenzene, p-aminoazobenzene, azobenzene and quantitative detection of SOG. Experimental results revealed that azo compounds could quench the fluorescent intensity of N-CDs. Owing to various azo compounds showing different affinities to N-CDs, the sensor array exhibited different fluorescence quenching changes, which were further analyzed with principal component analysis to discriminate azo compounds. The sensor array was able to differentiate and recognize diverse concentrations of azo compounds from 0.25 to 2 mg/L. Simultaneously, a variety of factors affecting the detection of SOG were optimized. Under the optimized conditions, the sensor showed excellent stability and sensitivity. The sensor possessed marvelous linearity in the range of 0.1-1 mg/L and 1-4 mg/L and the detection limit was 27.82 μg/L. Spiked recoveries of 90.8-98.2 % were attained at spiked levels of 0.2 mg/L and 1 mg/L, demonstrating that the constructed fluorescence sensor was dependable and feasible for sensing SOG in environmental water samples.
PubMed: 38640659
DOI: 10.1016/j.jcis.2024.04.109 -
Anaerobe Oct 2023We set out to survey the capacities of bacterial isolates from the human gut microbiome to reduce common azo food dyes in vitro.
OBJECTIVES
We set out to survey the capacities of bacterial isolates from the human gut microbiome to reduce common azo food dyes in vitro.
METHODS
A total of 206 strains representative of 124 bacterial species and 6 phyla were screened in vitro using a simple azo dye decolorization assay. Strains which showed azoreductive activity were characterized by studies of azoreduction kinetics and bacterial growth.
RESULTS
Several groups of gut bacteria, including ones not previously associated with azoreduction, reduced one or more of the four azo food dyes commonly used in Canada: Allura Red, Amaranth, Sunset Yellow, and Tartrazine. Strains within some species differed in their azoreductive capabilities. Some strains displayed evidence of effects on growth related to the presence of azo dyes and/or the products of their azoreduction.
CONCLUSION
The continued widespread use of food azo dyes requires re-evaluation in light of the potential for disturbance of the gut microbial ecosystem resulting from azoreduction and the possibility of consequences for human health.
Topics: Humans; Gastrointestinal Microbiome; Ecosystem; Azo Compounds; Bacteria; Coloring Agents
PubMed: 37769703
DOI: 10.1016/j.anaerobe.2023.102783