Phenazine Derivatives Research Articles

Introducing a green nanocatalytic process toward the synthesis of benzo[a]pyrano-[2,3-c]phenazines utilizing copper oxide quantum dot-modified core-shell magnetic mesoporous silica nanoparticles as high throughput and reusable nanocatalysts.

In this contribution, a green, simple, efficient, and straightforward nanocatalytic process was developed for the synthesis of benzo[a]pyrano[2,3-c]phenazine derivatives under mild thermal conditions. In this regard, the copper oxide quantum dot-modified magnetic silica mesoporous nanoparticles (M-MSNs/CuO(QDs)) were synthesized by surface modification of M-MSNs with CuO QDs to prepare a highly powerful magnetic core–shell nanocatalyst. The prepared nanocatalyst was then characterized for its functionality, size, morphology, elemental composition, surface area, crystallinity, and magnetic properties. Afterwards, it was applied for the synthesis of benzo[a]pyrano[2,3-c]phenazine derivatives under green reaction conditions. The factors affecting the reaction yield were optimized by the one-factor-at-a-time optimization method. Under obtained optimal conditions, the developed method showed a reaction yield range as high as 86–95% for different derivatives. The reusability studies were performed for indexing the cycling stability of the prepared magnetic nanocatalyst. The results exhibited that the catalytic efficiency of the nanocatalyst was saved for at least 5 operational times, showing high cycling stability of M-MSNs/CuO(QDs). Finally, the catalytic performances of the nanocatalyst was compared with the reported ones, revealing that the M-MSNs/CuO(QDs) presents very better performances toward the synthesis of benzo[a]pyrano[2,3-c]phenazine derivatives than the reported ones.

Stereo-electronic effect of the perfluoropropyl group on the solid-state molecular packing of isomeric dibenzo[a,c]phenazine derivatives

We report here the synthesis, characterization, and crystal structures of three perfluoropropylated dibenzo[a,c]phenazine constitutional isomers, in which the only difference among them was the positions of the perfluoropropyl substituents.

Tuning non-radiative decay channelsviasymmetric/asymmetric substituent effects on phenazine derivatives and their phototherapy switch between dynamic and thermal processes

Two emitters based on substituent effects exhibited different and competitive non-radiative decay processes, that was intersystem crossing and thermal deactivation, and excellent phototherapy achievement was realized by the two corresponding processes.

Design strategies and applications of novel functionalized phenazine derivatives: a review

This review comprehensively summarized and discussed the recent achievements towards innovative strategies, excellent properties and promising application to create functional materials based on phenazine derivatives in optical sensing and electrochemistry.

NOVEL QUINOXALINE DERIVATIVES: SYNTHESIS, THERMAL, PHOTO PHYSICAL STUDIES AND BIOLOGICAL ACTIVITY

Several studies have shown that derivatives of Isatin, Phenazine and Phenanthrenedione have a broad spectrum of biological activity. A large number of pharmacology active species can be synthesized from these precursors. Some of its derivatives are molecules with planar structure, a condition that displays the good capacity to interact with DNA by intercalation. Based on this information, we are designing synthesized N-Heteroacene derivatives and testing potential drugs as antimicrobial, antifungal and anticancer agents. The synthesized N-Heteroacene derivatives are characterized by IR, NMR, Mass spectrum, thermal and photophysical studies

Computational design of phenazine derivative molecules as redox-active electrolyte materials in alkaline aqueous organic flow batteries

DFT calculations are used to reveal the structure–property relationships of the redox potentials and solvation free energies of phenazine derivatives for alkaline aqueous organic flow batteries.

Microwave-Assisted Multi-Component Green Synthesis of Benzo[α]furo[2, 3-c]phenazine Derivatives via a Magnetically-Separable Fe3O4@rGO@ZnO-HPA Nanocatalyst under Solvent-Free Conditions

A novel and efficient method for the synthesis of benzo[α]furo[2, 3-c]phenazine derivatives by the reaction of benzo[a]phenazin-5-ol, Arylglyoxals, and methyl indole in the present Fe3O4@rGO@ZnO-HPA magnetic core-shell nanoparticles (MCNPs) under microwave reaction is reported. The catalyst was characterized by FT-IR, TEM, FESEM, XRD, AFM, hot-filtration, and VSM techniques. The advantages of a method are High yields, short reaction time (10–15 min), operational simplicity, absence of any tedious workup or purification, and avoidance of hazardous or toxic reagents/solvents are the salient features of this eco-friendly methodology.

Development of platforms for functional characterization and production of phenazines using a multi-chassis approach via CRAGE

Phenazines (Phzs), a family of chemicals with a phenazine backbone, are secondary metabolites with diverse properties such as antibacterial, anti-fungal, or anticancer activity. The core derivatives of phenazine, phenazine-1-carboxylic acid (PCA) and phenazine-1,6-dicarboxylic acid (PDC), are themselves precursors for various other derivatives. Recent advances in genome mining tools have enabled researchers to identify many biosynthetic gene clusters (BGCs) that might produce novel Phzs. To characterize the function of these BGCs efficiently, we performed modular construct assembly and subsequent multi-chassis heterologous expression using chassis-independent recombinase-assisted genome engineering (CRAGE). CRAGE allowed rapid integration of a PCA BGC into 23 diverse γ-proteobacteria species and allowed us to identify top PCA producers. We then used the top five chassis hosts to express four partially refactored PDC BGCs. A few of these platforms produced high levels of PDC. Specifically, Xenorhabdus doucetiae and Pseudomonas simiae produced PDC at a titer of 293 mg/L and 373 mg/L, respectively, in minimal media. These titers are significantly higher than those previously reported. Furthermore, selectivity toward PDC production over PCA production was improved by up to 9-fold. The results show that these strains are promising chassis for production of PCA, PDC, and their derivatives, as well as for function characterization of Phz BGCs identified via bioinformatics mining.

Novel approach of phenazine derivatives isolation from Pseudomonas culture medium

Produced by some microorganisms phenazine antibiotics are an attractive alternative to chemical pesticides and conventional drugs. Existing methods for phenazine extraction possess low yield and impede further use.A newly developed method of phenazine derivatives extraction based on solid-phase extraction resulted in up to 13 times increase in phenazine derivatives yield compared to the “classic” liquid-liquid extraction procedure. Moreover, such approach allows obtaining of separate crystals of pure phenazine compounds from the culture medium of Pseudomonas chlororaphis subsp. aurantiaca B-162. Significance and impact of studyPhenazine metabolites have significant potential in agriculture and medicine. A novel highly effective method of phenazine extraction and purification can be employed in the synthesis of its derivatives or directly for agricultural or medical uses.

Advances in Phenazines over the Past Decade: Review of Their Pharmacological Activities, Mechanisms of Action, Biosynthetic Pathways and Synthetic Strategies

Phenazines are a large group of nitrogen-containing heterocycles, providing diverse chemical structures and various biological activities. Natural phenazines are mainly isolated from marine and terrestrial microorganisms. So far, more than 100 different natural compounds and over 6000 synthetic derivatives have been found and investigated. Many phenazines show great pharmacological activity in various fields, such as antimicrobial, antiparasitic, neuroprotective, insecticidal, anti-inflammatory and anticancer activity. Researchers continued to investigate these compounds and hope to develop them as medicines. Cimmino et al. published a significant review about anticancer activity of phenazines, containing articles from 2000 to 2011. Here, we mainly summarize articles from 2012 to 2021. According to sources of compounds, phenazines were categorized into natural phenazines and synthetic phenazine derivatives in this review. Their pharmacological activities, mechanisms of action, biosynthetic pathways and synthetic strategies were summarized. These may provide guidance for the investigation on phenazines in the future.

A selective and stable vapochromic system constructed by pillar[5]arene-based host–guest interactions

The development of new strategies for the construction of highly selective and stable vapochromic system is still in great demand. Here, we present a highly selective and stable vapochromic system constructed by pillar[5]arene-based host–guest interactions between a pillar[5]arene (EtP5) and a phenazine derivative. The present material in this work showed specific selective responsiveness to chloroform vapor. The resultant dark orange solid sample was highly stable, which can maintain the color in air for at least two months at room temperature. Moreover, CHCl3 vapor responsive thin film and light-emitting diode (LED) was successfully prepared by coating the EtP5⊃1 complex on a glass sheet and a commercially available UV-LED. This work provided a new approach for the design and construction of selective and stable vapochromic systems with obvious color changes using pillar[5]arene-based host–guest interactions.

Triazolyl Dibenzo[a,c]phenazines Stabilize Telomeric G-quadruplex and Inhibit Telomerase.

We herein report the synthesis and biophysical evaluation of triazolyl dibenzo[a,c]phenazine derivatives as a novel class of G-quadruplex ligands. The aromatic core facilitates π-π interaction and the flexible, protonatable side chains interact with the phosphate backbone of DNA via electrostatic interactions. Förster resonance energy transfer (FRET) melting assay and isothermal titration calorimetry (ITC) studies suggest that these ligands show binding preference for the hTELO G-quadruplex over G-quadruplexes found in the promoter region of various oncogenes and duplex DNA. The in vitro telomeric repeat amplification protocol (Q-TRAP) assay reveals that these ligands reduce telomerase activity in cancer cells.

Variations in Complementary Hydrogen Bonds Direct Assembly Patterns of Isosteric Polyheteroaromatics at Surfaces

Intermolecular interactions guide self-assembly on the surface. Precise control over these interactions by rational design of the molecule should allow fine control over the self-assembly patterns. Functional groups installed for electronic modulation often induce significant changes in the molecular dimensions, thereby disrupting the original assembly pattern. To overcome this challenge, we have employed a family of isosteric phenazine derivatives, DHP, DAP, and DBQD, to investigate the impacts of hydrogen bonding on two-dimensional molecular self-assembly. While these molecules are similar in size and chemical composition, the strength and directionality of hydrogen bonding differ significantly depending on the chemical structure of donor-acceptor pairs and prototropic tautomerization from positional isomerism. Scanning tunneling microscopy (STM) characterization of the assembled structures on Ag(111), Au(111), and Cu(100) surfaces revealed that minimal changes in molecular structure have a profound impact on the self-assembly patterns. While DHP exhibits highly ordered and robust assemblies, DAP and DBQD show either spatially confined or ill-defined assemblies. In conjunction with hydrogen bonding, prototropic tautomerism is a potent strategy to modulate molecular 2D lattices on surfaces.

Vibratile Dihydrophenazines with Controllable Luminescence Enabled by Precise Regulation of π-Conjugated Wings

Vibratile Dihydrophenazines with Controllable Luminescence Enabled by Precise Regulation of π-Conjugated Wings

Influence of the amine donor on hybrid guanidine-stabilized Bis(μ-oxido) dicopper(III) complexes and their tyrosinase-like oxygenation activity towards polycyclic aromatic alcohols

The tyrosinase-like activity of hybrid guanidine-stabilized bis(μ-oxido) dicopper(III) complexes [Cu2(μ-O)2(L)2](X)2 (L = 2-{2-((Diethylamino)methyl)phenyl}-1,1,3,3-tetramethylguanidine (TMGbenzNEt2, L2) and 2-{2-((Di-isopropylamino)methyl)phenyl}-1,1,3,3-tetramethylguanidine (TMGbenzNiPr2, L3); X = PF6−, BF4−, CF3SO3−) is described. New aromatic hybrid guanidine amine ligands were developed with varying amine donor function. Their copper(I) complexes were analyzed towards their ability to activate dioxygen in the presence of different weakly coordinating anions. The resulting bis(μ-oxido) species were characterized at low temperatures by UV/Vis and resonance Raman spectroscopy, cryo-ESI mass spectrometry and density functional theory calculations. Small structural changes in the ligand sphere were found to influence the characteristic ligand-to-metal charge transfer (LMCT) features of the bis(μ-oxido) species, correlating a redshift in the UV/Vis spectrum with weaker N-donor function of the ligand. DFT calculations elucidated the influence of the steric and electronic properties of the bis(μ-oxido) species leading to a higher twist of the Cu2O2 plane against the CuN2 plane and a stretching of the Cu2O2 core. Despite their moderate stability at −100 °C, the bis(μ-oxido) complexes exhibited a remarkable activity in catalytic oxygenation reactions of polycyclic aromatic alcohols. Further the selectivity of the catalyst in the hydroxylation reactions of challenging phenolic substrates is not changed despite an increasing shield of the reactive bis(μ-oxido) core. The generated quinones were found to form exclusively bent phenazines, providing a promising strategy to access tailored phenazine derivatives.

Ce immobilized 1H-pyrazole-3,5-dicarboxylic acid (PDA) modified CoFe2O4: A potential magnetic nanocomposite catalyst towards the synthesis of diverse benzo[a]pyrano[2,3-c]phenazine derivatives

A great deal of modern material research involves the design and synthesis of biomolecular functionalized green catalysts. In this context, we have engineered a novel nanocomposite material by functionalizing 1H-pyrazole-3,5-dicarboxylic acid ligand over CoFe2O4 NPs and subsequently immobilized Ce ions over it. The ligand anchors the metal ion in 1:2 fashion through its two carboxylic acid functions. The as-synthesized material was meticulously characterized by using a wide range of physicochemical techniques like FT-IR, VSM, SEM, TEM, EDX, elemental mapping, XRD, TGA, N2 adsorption-desorption and BET surface area analysis. The nanocomposite was catalytically explored in the synthesis of an array of biologically important benzo[a]pyrano[2,3-c]phenazine derivatives by condensing 2-hydroxynaphthalene-1,4-dione, o-phenylenediamines, malononitrile and different aryl aldehydes under green conditions. A diverse range of products was synthesized with outstandingyields in short reaction times. Due to inherent magnetism, the catalyst was recovered from the reaction magnetic decantation and recycled for six consecutive runs with a nominal decrease in yield.

Study of modulating opto-electrochemical properties in Suzuki coupled phenazine derivatives for organic electronics

Study of modulating opto-electrochemical properties in Suzuki coupled phenazine derivatives for organic electronics

Benzo[a]phenazine derivatives: Promising scaffolds to combat resistant Mycobacterium tuberculosis.

The continuous emergence of resistant Mycobacterium tuberculosis keeps tuberculosis (TB) treatment options still insufficient, and new therapeutic alternatives are urgently needed. Considering the antimycobacterial activity of phenazine derivatives previously reported by our research group, we aimed to explore possible applications to circumvent the resistance in M. tuberculosis. Firstly, we evaluated the antimicrobial activity of seven benzo[a]phenazine derivatives against eleven M. tuberculosis strains: ten resistant and one susceptible (H37 Rv). Then, we determined the cytotoxicity of benzo[a]phenazine derivatives and investigated the possible mechanism of action of the most promising compound. Among them, compound 10 was the only one active against all strains evaluated, with a minimum inhibitory concentration between 18.3 and 146.5µM. For some resistant strains, this compound showed antimicrobial activity higher than rifampicin and it was also active against MDR strains, indicating an absence of cross-resistance with anti-TB drugs. Also, 10 showed a pharmacological safety for further in vivo studies and its mechanism of action seems to be related to oxidative stress. Thus, our findings indicate that benzo[a]phenazine derivatives are promising scaffolds for the development of new anti-TB drugs, mainly focusing on the treatment of resistant TB cases.

Acid-base regulation the reversible transformation of novel phenazine derivatives and serving as biomarker for tracing acidity change in living cell and mice

Achieving a fluorescence sensor with controllable regulation on the morphology and optical properties is a tough challenge, despite their great promises acting as biomarker for monitoring the physiological processes. Herein, we successfully developed and synthesized an original phenazine derivatives (TD-B) with controllable morphological transformation and optical performance through acid-base regulation, acting as a biomarker for visually tracing acid change in living cell and mice. In this work, the lactic acid (LA) was selected as the precursor of acidic biomass, and the prominent reversible performance of which was systematically investigated. The results suggested that the transformative behaviour of TD-B was realized with controllability not only presenting in vitro test, but also reflecting in the living imaging analysis, which disclosed great potential applied for monitoring and imaging LA in living cell and mice. 11*Corresponding author Tel: +086 9317973191; E-mail address: weitaibao@126.com. It is hoped that this design approach could lay a solid foundation for the further exploitation of a variety of biomarkers, and show potential application prospects in the diagnosis of some clinical diseases and the design of controlled drug release platform.

Mechanistic insights into 5-lipoxygenase inhibition by pyocyanin: a molecular docking and molecular dynamics study

Pyocyanin, a redox-active phenazine pigment produced by Pseudomonas aeruginosa, inhibits 5-lipoxygenase (5-LOX) activity. However, whether pyocyanin can directly block the enzymatic activity by binding at the active site still remains a question because of its ability to produce superoxide radicals and H2O2. With the objective of characterizing this mechanism, we carried out molecular docking and molecular dynamics simulations and performed Molecular Mechanics Poisson-Boltzmann surface area (MMPBSA) binding energy studies. The results of the study revealed that pyocyanin is dynamically stable at the active site of 5-LOX and its MMPBSA binding energy (−84.720 kJ/mol) is comparable to that of the 5-LOX standard inhibitor zileuton (−72.729 kJ/mol). Similar studies using three other phenazine derivatives − 1-hydroxyphenazine, phenazine-1-carboxylic acid and phenazine-1-carboxamide – also showed encouraging results. In light of this evidence, we postulate as a proof of concept that pyocyanin and these phenazine derivatives have the potential to inhibit 5-LOX activity by directly binding at the active site and blocking enzymatic catalysis of the substrate. Considering the potential of 5-LOX inhibitors in inflammatory diseases such as asthma and rheumatoid arthritis, the findings of this study open up the exploration of phenazine derivatives in structure-based drug design against 5-LOX. Communicated by Ramaswamy H. Sarma