Phenazine Derivatives Research Articles

Synthesis and biological evaluation of novel benzo[a]pyridazino[3,4-c]phenazine derivatives

A convenient microwave-assisted one-pot four-component synthetic approach was developed en route to novel functionalized benzo[a]pyridazino[3,4-c]phenazine derivatives starting from 2-hydroxy-1,4-naphthoquinone, aromatic aldehydes, methyl hydrazine and o-phenylenediamine. Nine new derivatives were successfully synthesized and subsequently evaluated in terms of their biological profiles. The results revealed good cytotoxic activities of compounds 6a, 6h against KB, HepG2, Lu1 and MCF7 human cancer cell lines. Besides that, compound 6d exhibited promising antimicrobial activities toward Staphylococcuc aureus and Bacillus subtilis bacterial strains with IC50 < 6 μM.

Simulating the redox potentials of unexplored phenazine derivatives as electron mediators for biofuel cells

In this research, we aimed to establish a guideline for designing electron mediators suitable for biofuel cells. A redox potential simulator was fabricated by combining density functional theory calculation and experiment, allowing us to select molecules with appropriate redox potentials efficiently. Previously, mediators have been developed depending on the trials and errors; thus, our strategy will speed up the development of biofuel cells with outstanding performances.

Enhanced recovery of nitrous oxide from incineration leachate in a microbial electrolysis cell inoculated with a nosZ-deficient strain of Pseudomonas aeruginosa

High concentrations of nitrous oxide were recovered from partial nitrification treated leachate in a microbial electrolysis cell (MEC) inoculated with a nosZ-deficient strain of Pseudomonas aeruginosa. N2O conversion efficiencies > 90% were achieved when a potential of 0.8 V was applied to the MEC. The ΔnosZ strain was enriched in the 0.8 V MEC, but Achromobacter dominated the non-current control. Nitric oxide reductase genes were highly expressed by ΔnosZ cells growing in the 0.8 V MEC, consistent with enhanced nitrous oxide production rates. Concentrations of phenazine derivatives and transcripts from phenazine biosynthesis genes were also high in the 0.8 V MEC. Phenazine derivatives are known to act as electron shuttles, enhance biofilm formation, and help ward off competitors, thereby increasing the survivability of the ΔnosZ strain in the MEC. These results show that applied current stabilized growth of the ΔnosZ strain in the reactor and allowed it to sustainably generate high concentrations of nitrous oxide.

Design and Fabricating biogenic amine-responsive platform based on self-assembly property of phenazine derivative for visual monitoring of meat spoilage

Abstract Smart label serving as a response to a particular stimulus (e.g., biogenic amines) endow great potential to monitor the storage conditions and food freshness. Therefore, the development of smart food packaging for supervising the degree of food decay in real-time is of great importance in food safety. To this endeavor, herein we successfully fabricated a novel biogenic amine-responsive platform (P-N) based on supramolecular host-guest interaction, exploiting self-assembly properties of phenazine derivatives (PY) and naphthalene diamide (NDI) induced by hydrogen bond. Taking advantage of this feature, we investigated the prominent performance of this biogenic amine-responsive platform (P-N), involving in feasible fabrication pathway, specific response to biogenic amine, persistent stability and further application as a smart label for motoring meat spoilage. Those observations demonstrated that the P-N could self-assembly into well-organized rodlike structure showing strong AIE effect, not only exhibiting high sensitivity and great potential in the practical application, but also yielding an excellent proof-of-concept smart label in supervising the meat spoilage. Such a novel fabrication strategy is expected to provide some guidance to develop various smart food packaging label for motoring food freshness.

Discovery of novel obovatol-based phenazine analogs as potential antifungal agents: synthesis and biological evaluation in vitro

Abstract To explore candidate fungicides from plant secondary metabolites, 16 novel obovatol-type phenazine derivatives were semi-synthesized from obovatol isolated from the leaves of Magnolia obovata Thunb. The antifungal activity of synthesized compounds was investigated in vitro against four phytopathogenic fungi using the spore germination method. The bioassay results showed that eight derivatives (8b, 8g, 8h–k, 8i′, and 8k′) exhibited better antifungal activity against Fusarium solani than two positive controls, especially compounds 8b (IC50 = 64.61 μg mL−1) and 8i′ (IC50 = 79.97 μg mL−1) showed pronounced inhibition of spore germination activity against F. solani. They could be used as lead compounds for further structural optimization. Additionally, the preliminary structure-activity relationships (SARs) illustrated that the introduction of a benzene ring monosubstituted with electron-withdrawing groups into the obovatol scaffold could lead to potentially antifungal compounds.

Design, synthesis and biological evaluations of diverse Michael acceptor-based phenazine hybrid molecules as TrxR1 inhibitors

A series of novel phenazine derivatives (1~27) containing the Michael acceptor scaffolds were designed and synthesized in this study. Some compounds exhibited selective cytotoxicity against Bel-7402 cancer cell line in vitro, in which compound 26 were found to have the best antiproliferative activity. Meanwhile, compound 26 showed no obvious cell toxicity against human normal liver epithelial L02 cells, which means this compound possessed a better safety potential. In the following research, compound 26 was verified to inhibit TrxR1 enzyme activity, ultimately resulting in cellular molecular mechanism events of apoptosis including growth of intracellular ROS level, depletion of reduced Trx1, liberation of ASK1 and up-regulation of p38, respectively. Together, all these evidences implicated that compound 26 acted as the TrxR1 inhibitor against Bel-7402 cells, and could activate apoptosis through the ROS-Trx-ASK1-p38 pathway.

Room temperature stable multitalent: highly reactive and versatile copper guanidine complexes in oxygenation reactions

Inspired by the efficiency of natural enzymes in organic transformation reactions, the development of synthetic catalysts for oxygenation and oxidation reactions under mild conditions still remains challenging. Tyrosinases serve as archetype when it comes to hydroxylation reactions involving molecular oxygen. We herein present new copper(I) guanidine halide complexes, capable of the activation of molecular oxygen at room temperature. The formation of the reactive bis(µ-oxido) dicopper(III) species and the influence of the anion are investigated by UV/Vis spectroscopy, mass spectrometry, and density functional theory. We highlight the catalytic hydroxylation activity towards diverse polycyclic aromatic alcohols under mild reaction conditions. The selective formation of reactive quinones provides a promising tool to design phenazine derivatives for medical applications.Graphic abstract

Identification of a Novel Bioactive Phenazine Derivative and Regulation of phoP on Its Production in Streptomyces lomondensis S015.

Natural phenazines are a class of multifunctional secondary metabolites of bacteria that play an important role in the biocontrol of plant pathogens. In this paper, a novel bioactive phenazine derivative was isolated from Streptomyces lomondensis S015 through silica gel chromatography and preparative high-performance liquid chromatography (HPLC). The structure was identified as 1-carboxyl-6-formyl-4,7,9-trihydroxy-phenazine (CFTHP) by NMR spectroscopy in combination with ultraperformance liquid chromatography & mass spectrometry (UPLC-MS). CFTHP could inhibit Pythium ultimum, Rhizoctonia solani, Septoria steviae, and Fusarium oxysporum f. sp. niveum with minimal inhibitory concentration (MIC) values of 16, 32, 16, and 16 μg/mL, respectively. A global regulatory gene phoP could positively regulate CFTHP biosynthesis since its production was 3.0-fold enhanced by phoP overexpression and inhibited by phoP deletion in Streptomyces lomondensis S015. These studies illustrated the potential of CFTHP as a promising biopesticide and provided a reference for phenazine production improvement.

Profiling of antimicrobial metabolites of plant growth promoting Pseudomonas spp. isolated from different plant hosts.

The online version contains supplementary material available at 10.1007/s13205-020-02585-8.

Synthesis of benzo[a]furo[2, 3-c]phenazine derivatives through an efficient, rapid and via microwave irradiation under solvent-free conditions catalyzed by H3PW12O40@Fe3O4-ZnO for high-performance removal of methylene blue

A rapid, one-pot synthesis of eight benzo[a]furo[2,3-c]phenazine derivatives has been achieved in moderate to good yields in good yields via a multi-component of 2-hydroxynaphthalene-1,4-dione, arylglyoxal, indole (H, CH3) in the presence of H3PW12O40@Fe3O4-ZnO magnetic core-shell nanoparticles (MCNPs) under solvent-free conditions using microwave irradiation. The catalyst was synthesised and characterised by X-ray diffraction, EDX, TEM, FESEM, TGA, VSM and atomic force microscope. As an application for the synthesised nanocatalyst, degradation of methylene blue as heavy-mass organic pollution was measured. These results showed advantages for synthesis, such as mild reaction conditions, low energy consumption and economically affordable.

Synthesis of novel regioisomeric phenanthro[a]phenazine derivatives through the SNAr strategy and their self-assembly into columnar phases

Synthesis and characterization of novel discotic liquid crystalline regioisomers for optoelectronic applications.

Synthesis of novel π-extended D–A–D-type dipyrido[3,2-a:2′,3′-c]phenazine derivatives and their photosensitized singlet oxygen generation

Electron donor–acceptor–donor (D–A–D) π-conjugated molecules based on dipyrido[3,2-a:2′,3′-c]phenazine (dppz) were developed as photosensitizers for singlet oxygen generation.

A novel photochemical sensor based on quinoline-functionalized phenazine derivatives for multiple substrate detection

A novel photochemical sensor based on quinoline-functionalized phenazine derivatives for highly sensitive detection of multiple substrates (l-Arg, CO2, and pH) was designed and synthesized.

Fabrication of a solid sensor based on a phenazine derivative film for enhancing the sensing properties of biogenic amine and applying for monitoring shrimp freshness

In practical applications, fixing a fluorescent sensor on a solid composite film matrix can settle the boundaries of keeping the sensor in the solution state.

Elevation of the serotonin-derived quinone, tryptamine-4,5-dione, in the intestine of ICR mice with dextran sulfate-induced colitis.

Inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis, are chronic inflammatory disorders associated with oxidative stress. The intestines produce 5-hydroxytryptamine that may negatively affect disease state under inflammatory conditions when overproduced. 5-Hydroxytryptamine is a substrate for myeloperoxidase and is converted into reactive tryptamine-4,5-dione. Here, an experimental colitis model was established through oral administration of 5% dextran sulfate sodium to ICR mice for 7 days. Furthermore, the formation of tryptamine-4,5-dione in the colorectal mucosa/submucosa and colorectal tissue was analyzed by chemical and immunochemical methodologies. First, free tryptamine-4,5-dione in the homogenate was chemically trapped by o-phenylenediamine and analyzed as the stable phenazine derivative. Tryptamine-4,5-dione localization as adducted proteins in the colorectal tissue was immunohistochemically confirmed, and as demonstrated by both methods, this resulted in the significant increase of tryptamine-4,5-dione in dextran sulfate sodium-challenged mice compared with control mice. Immunohistochemical staining confirmed tryptamine-4,5-dione-positive staining at the myeloperoxidase accumulation site in dextran sulfate sodium-challenged mice colorectal tissue. The tryptamine-4,5-dione locus in the mice was partly matched with that of a specific marker for myeloperoxidase, halogenated tyrosine. Overall, the results possibly indicate that tryptamine-4,5-dione is generated by neutrophil myeloperoxidase in inflammatory tissue and may contribute to the development of inflammatory bowel disease.

New phenazine based anolyte material for high voltage organic redox flow batteries.

Herein, we report the synthesis and investigation of a novel phenazine derivative M1 with oligomeric ethylene glycol ether substituents as a promising anolyte material for non-aqueous organic redox flow batteries (RFBs). The designed material undergoes a reversible and stable reduction at -1.72 V vs. Ag/AgNO3 and demonstrates excellent (>2.5 M) solubility in MeCN. A non-aqueous organic redox flow battery assembled using the novel phenazine derivative as an anolyte and a substituted triarylamine derivative as a catholyte exhibited high specific capacity (∼93% from the theoretical value), >95% Coulombic efficiency, 65% utilization of active materials and good charge-discharge cycling stability.

Real‐Time Visual Monitoring of Kinetically Controlled Self‐Assembly

AbstractThe construction of artificial structures through hierarchical self‐assembly based on noncovalent interactions, as well as monitoring during the self‐assembly process, are important aspects of dynamic supramolecular chemistry. Herein we describe the complex dynamics of chiral N,N′‐diphenyl dihydrodibenzo[a,c]phenazine derivatives (S)/(R)‐DPAC, whose different assemblies were found to have distinct optical and morphological characteristics. With ratiometric fluorescence originating from vibration‐induced emission (VIE), the self‐assembly process from kinetic traps to the thermodynamic equilibrium state could be monitored in real time by optical spectrometry. During the morphology transformation from particles to nanobricks, strong circularly polarized luminescence was induced with glum=1.6×10−2. The excited‐state characteristics of the self‐assemblies enabled investigation of the relationship between molecular aggregation and conformational change, thus allowing effective monitoring of the sophisticated supramolecular self‐assembly process.

Real-Time Visual Monitoring of Kinetically Controlled Self-Assembly.

The construction of artificial structures through hierarchical self-assembly based on noncovalent interactions, as well as monitoring during the self-assembly process, are important aspects of dynamic supramolecular chemistry. Herein we describe the complex dynamics of chiral N,N'-diphenyl dihydrodibenzo[a,c]phenazine derivatives (S)/(R)-DPAC, whose different assemblies were found to have distinct optical and morphological characteristics. With ratiometric fluorescence originating from vibration-induced emission (VIE), the self-assembly process from kinetic traps to the thermodynamic equilibrium state could be monitored in real time by optical spectrometry. During the morphology transformation from particles to nanobricks, strong circularly polarized luminescence was induced with glum =1.6×10-2 . The excited-state characteristics of the self-assemblies enabled investigation of the relationship between molecular aggregation and conformational change, thus allowing effective monitoring of the sophisticated supramolecular self-assembly process.

Metabolic Engineering of Pseudomonas chlororaphis Qlu-1 for the Enhanced Production of Phenazine-1-carboxamide.

Phenazine-1-carboxylic acid (PCA), the primary active ingredient of Shenqinmycin, was awarded the China Pesticide Certificate in 2011 due to its excellent antibacterial action. Phenazine-1-carboxamide (PCN) is a derivative of PCA, which is modified by the phzH gene, and its anti-bacterial effect is better than that of PCA. At present, PCN can be produced via Pseudomonas fermentation using an opportunistic pathogen, Pseudomonas aeruginosa. Qlu-1 is an environmentally friendly strain of Pseudomonas chlororaphis that can produce phenazine derivatives. We replaced the phzO gene with the phzH gene from P. aeruginosa to achieve PCN accumulation. Different strategies were used to enhance PCN production: knocking out of negative regulatory factors, enhancing the shikimate pathway by gene overexpression and gene knocking, and using fed-batch fermentation. Finally, an engineered strain of P. chlororaphis was produced, which produced 11.45 g/L PCN. This achievement indicates that Qlu-1 could be modified as a potential microbial cell factory for PCN production by metabolic engineering.

Fabrication of a luminescence-silent oxidation platform based on phenazine derivatives for monitoring and imaging ascorbic acid in living cells and real sample

Small-molecule reactive biomolecules serve essential roles in cell signaling and thus are involved in both human health and disease. Herein, a novel luminescence-silent oxidation probe (2PO-H@Fe) for monitoring and imaging of reductive biomolecule (ascorbic acid) was presented on basis of redox reaction. Taking advantage of this feature, we have investigated the prominent sensing performance of this luminescence-silent oxidation sensor platform, involving in feasible fabrication pathway, specific response to ascribe acid (Vc), persistent stability and further sensing application. The observations demonstrated that the probe (2PO-H@Fe) could not only exhibit high sensitivity and selectivity for detecting Vc, but also have great potential in the practical application, gaining excellent recoveries in the fresh fruits. More importantly, the 2PO-H@Fe could perceive Vc in the living Hela cells and achieved admirable sensing performance. Such a novel fabrication strategy is expected to offer some guidance to develop various luminescence-silent systems as “turn-on” sensors for examining target biomolecule.