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Two asymmetric donor‐acceptor‐donor’ (D‐A‐D’) type deep blue thermally activated delayed fluorescence (TADF) emitters, namely PAO‐1 and PAO‐2, are developed with highly rigid 10‐(pyridin‐2‐yl)acridin‐9(10H)‐one (PAO) as acceptor (A). PAO is characterized by the 3,6‐sites carbon atoms that are void to its own HOMO and the deeper HOMO‐2 of PAO acceptor rather than its HOMO is involved in the HOMO of the TADF emitters. Such D‐void‐A connecting mode favors to lower the molecular HOMO and generate short‐wavelength fluorescence by enlarging the bandgap of the TADF emitters. Two different carbazole donors are utilized in the asymmetric D‐A‐D’ type emitters, which not only keep the deep blue emission but also enhance the oscillator strength (f) for faster radiative transition rates (krs > 108 s−1) and slightly slow the intersystem crossing (ISC) rates (kISCs) and reverse ISC (kRISCs) than the symmetric PAO‐0, which can reduce exciton trap in the conversion cycles between singlet and triplet excitons. The deep blue OLEDs of PAO‐1 and PAO‐2 exhibit external quantum efficiencies (EQEs) of 32.5% and 30.1% with CIE (0.15, 0.10) and (0.15, 0.11) and low‐efficiency roll‐offs. These findings provide a design strategy for developing highly efficient deep‐blue TADF emitters. [ABSTRACT FROM AUTHOR]

Porous organic polymers (POPs) are emergent tailor‐made materials, which can be accessed by covalent polymerization of diligently designed molecular building blocks in a bottom‐up fashion. Acridone, a well‐known chromophore that undergoes intersystem crossing (ISC) with near‐unity quantum yield akin to benzophenone, was structurally elaborated into a building block and subjected to Friedel‐Crafts polyalkylation to afford a series of POPs, namely, Ac‐MePOP, Ac‐OMePOP, and Ac‐CBPOP. These POPs exhibit remarkable porosity and significant absorption in the visible region. Of the three polymers, Ac‐CBPOP with the highest BET surface area of ca. 1027 m2/g is shown to serve as an excellent heterogeneous photocatalyst for visible light‐mediated oxidative transformations, that is, oxidative coupling of benzylamines to imines and cyclocondensation of o‐phenylenediamines with aldehydes to benzimidazoles under oxygen atmosphere. It is further shown that Ac‐CBPOP can be reused for several reaction cycles without any loss of catalytic activity with its stability intact. Mechanistic studies show that 1O2 serves as the key reactive oxygen species, formed by the energy transfer from Ac‐CBPOP to 3O2, in the photocatalytic oxidation reactions. The results demonstrate the development of stable photocatalytic POP materials with tailor‐made properties by a bottom‐up covalent polymerization of programmed molecular building blocks. [ABSTRACT FROM AUTHOR]

The functionalization of small aromatic heterocycles is a straight and efficient method to access large polycyclic conjugated molecules. However, due to its unique reactivity, the derivatization of acridone usually gives the product in the angular shape and is difficult to obtain the linear ones. Here we report the direct functionalization of acridone to generate its linearly fused derivatives containing cyclobutadienoid via the palladium‐catalyzed arene‐(oxa)norbornene annulation followed by the dehydrated aromatization. The experimental characterizations demonstrate that the antiaromatic cyclobutadienoid ring can extend the molecular conjugation. Theoretical calculations reveal the weakened aromaticity of neighboring benzenoid rings of cyclobutadienoid with no influence on the electronic structure of central pyridone. The molecular stability is enhanced in comparison to that of linear acridone derivatives containing only six‐membered rings. [ABSTRACT FROM AUTHOR]

Ugandan Vepris trichocarpa sampled for this study yielded two undescribed acridone alkaloids here named trichouganda A (1), a 2‑methoxy derivative of evoxanthine (2), and trichouganda B (4), a 6‑methoxy derivative of 1,3,5-trimethoxy-10-methyl acridone. In addition, the known tecleanthine (3), tecleanone (5), and 1-(3,4-methylenedioxyphenyl)-propanetriol (6) were identified from the plant.

Because of environmental impact, there is a great need for chemosensors, especially for toxic heavy metals such as lead. The conventional instrumental analytical techniques rarely provide an available real-time sensing platform, thus the development of highly selective and stable synthetic chemosensor molecules is of great importance. Acridono-18-crown-6 ethers have such properties, and much research has proven their outstanding applicability in various supramolecular devices. In this present work, we aimed to enable their covalent immobilization capability by synthesizing functionalized derivatives while preserving the favored molecular recognition ability. Several new macrocycle analogues were synthesized, while synthetization difficulties and design aspects were also dealt with. The selectivity of the macrocycle analogues was studied using UV–Vis spectroscopy and compared with that of the parent compounds. The ultimate crown ether derivative showed high Pb2+-selectivity, reversibility (decomplexation by extraction with water) and stability. [ABSTRACT FROM AUTHOR]

Oropouche virus (OROV) is an emerging vector-borne arbovirus found in South America that causes Oropouche fever, a febrile infection similar to dengue fever. It has a high epidemic potential, causing illness in over 500,000 cases diagnosed since the virus was first discovered in 1955. Currently, the prevention of human viral infection depends on vaccination, but availability for many viruses is limited, and they are classified as neglected viruses. At present, there are no vaccines or antiviral treatments available. An alternative approach to limiting the spread of the virus is to selectively disrupt viral replication mechanisms. Here, we demonstrate the inhibitory effect of acridones, which efficiently inhibited viral replication by 99.9 % in vitro. To evaluate possible mechanisms of action, we conducted tests with dsRNA, an intermediate in virus replication, as well as MD simulations, docking, and binding free energy analysis. The results showed a strong interaction between FAC21 and the OROV endonuclease, which possibly limits the interaction of viral RNA with other proteins. Therefore, our results suggest a dual mechanism of antiviral action, possibly caused by ds-RNA intercalation. In summary, our findings demonstrate that a new generation of antiviral drugs could be developed based on the selective optimization of molecules.

Electron‐deficient acridones and in situ generated acridinium salts are reported as potent, closed‐shell photooxidants that undergo surprising mechanisms. When bridging acyclic triarylamine catalysts with a carbonyl group (acridones), this completely diverts their behavior away from open‐shell, radical cationic, 'beyond diffusion' photocatalysis to closed‐shell, neutral, diffusion‐controlled photocatalysis. Brønsted acid activation of acridones dramatically increases excited state oxidation power (by +0.8 V). Upon reduction of protonated acridones, they transform to electron‐deficient acridinium salts as even more potent photooxidants (*E1/2=+2.56–3.05 V vs SCE). These oxidize even electron‐deficient arenes where conventional acridinium salt photooxidants have thusfar been limited to electron‐rich arenes. Surprisingly, upon photoexcitation these electron‐deficient acridinium salts appear to undergo two electron reductive quenching to form acridinide anions, spectroscopically‐detected as their protonated forms. This new behaviour is partly enabled by a catalyst preassembly with the arene, and contrasts to conventional SET reductive quenching of acridinium salts. Critically, this study illustrates how redox active chromophoric molecules initially considered photocatalysts can transform during the reaction to catalytically active species with completely different redox and spectroscopic properties. [ABSTRACT FROM AUTHOR]

We present here a critical overview on the effects of the second heterocyclic subunit in a bisacridino-crown ether by the discussion of its role in modulating optochemical behavior and preference in molecular recognition. The preparation of a new bisacridono-crown ether is presented including synthetic difficulties, and its fluorescence properties and selectivity in formation of inclusion complexes with various cations are evaluated in the light of reported analogues. [ABSTRACT FROM AUTHOR]

Besides the peripheral modification, the introduction of heteroatoms to modulate the property of longer acenes with improved chemical stability has been extensively studied for their potential applications in organic electronics. However, the utilization of 4‐pyridone, a common unit in the air‐ and photo‐stable acridone and quinacridone, to decorate higher acenes with increased stability has not been realized yet. Here we present the synthesis of a series of monopyridone‐doped acenes up to heptacene via the palladium‐catalyzed Buchwald‐Hartwig amination of aniline and dibromo‐ketone. The effect of pyridone on the property of doped acenes were investigated experimentally and computationally. With the π‐extension of doped acenes, the pyridone ring shows the weakened conjugation and gradual loss of aromaticity. The doped acenes demonstrate enhanced stability in solution and maintain the electronic communication between the acene planes. [ABSTRACT FROM AUTHOR]

A total of 21 novel xanthone and acridone derivatives were synthesized using the reactions of 1,2,4-triazine derivatives with 1-hydroxy-3-methoxy-10-methylacridone, 1,3-dimethoxy-, and 1,3-dihydroxanthone, followed by optional dihydrotiazine ring aromatization. The synthesized compounds were evaluated for their anticancer activity against colorectal cancer HCT116, glioblastoma A-172, breast cancer Hs578T, and human embryonic kidney HEK-293 tumor cell lines. Five compounds (7a, 7e, 9e, 14a, and 14b) displayed good in vitro antiproliferative activities against these cancer cell lines. Compounds 7a and 7e demonstrated low toxicity for normal human embryonic kidney (HEK-293) cells, which determines the possibility of further development of these compounds as anticancer agents. Annexin V assay demonstrated that compound 7e activates apoptotic mechanisms and inhibits proliferation in glioblastoma cells. [ABSTRACT FROM AUTHOR]

Paratrimerin C is a natural acridone antioxidant that is also potent as an anti‐UV agent. The photophysical process of Paratrimerin C, including the absorption and emission and the excited state intramolecular proton transfer (ESIPT) mechanism, is studied herein with time‐dependent density functional theory. The solvent effect on ESIPT is studied for polar (water) and non‐polar (benzene) solvents employing the Integral Equation Formalism Polarization Continuum Model and adding up to three explicit molecules of solvent. The normal and tautomer forms of the Paratrimerin C at the ground‐ and excited‐state structures are studied at the M06‐2X/6‐311++G(d,p) level of theory. The potential energy curves along the reaction coordinates indicate that the ESIPT is a barrier‐less reaction, and the variation of OdOa distance in the excited state shows significant molecular structure deformation along the proton transfer process following the normal‐to‐tautomerism pathway. The obtained results suggest using of acridone derivatives as efficient and tunable fluorescence molecules besides their biological activities. [ABSTRACT FROM AUTHOR]

Acridone units were incorporated into the arylene–ethynylene structure as polar arene units. Cyclic trimers consisting of three acridone‐2,7‐diyl units and three 1,3‐phenylene units were synthesized by Sonogashira couplings via stepwise or direct route. X‐ray analysis revealed that the trimer had a nearly planar macrocyclic framework with a cavity surrounded by three carbonyl groups. In contrast, the corresponding tetramer had a nonplanar macrocyclic framework. 1H NMR measurements showed that the trimer formed a 1 : 1 complex as a macrocyclic host with dihydric phenol guests, and the association constants were determined to be ca. 1.0×103 L mol−1 for hydroquinone or resorcinol guests in CDCl3 at 298 K. The calculated structures of these complexes by the DFT method supported the presence of two sets of OH⋅⋅⋅O=C hydrogen bonds between the host and guest molecules. The spectroscopic data of the cyclic trimers and tetramers are compared with those of reference acridone compounds. [ABSTRACT FROM AUTHOR]

Applying the Ullmann synthesis, substituted aniline and o-halobenzoic acids are combined with potassium carbonate and copper powder to produce N- (substituted phenyl) anthranilic acids. Under the action of strong acids, the N-(substituted phenyl) anthranilic acids cyclize into acridone or substituted Acridones. In-vitro human cancer cell lines, in-vivo tumor xenograft models and genetically modified animal models are a few of the preclinical screening techniques that were used to evaluate the anticancer efficacy of the drug. The substance with a high binding score was produced, identified by the binding site for molecular docking and ligand binding was provided through the model's CASTp web server-revealed active site. Characterization was done using TLC, IR, NMR and mass spectroscopy. Their antioxidant and antimitotic properties were also analysed. DFT was used at the B3LYP/6-31G(d) level under solvent ethanol and a good correlation with experimental data was obtained. The synthesized compound showed significant activity.

By linking the carbazole unit to the nitrogen atom of acridone through phenyl or pyridyl, two compounds, named 10‐(4‐(9H‐carbazol‐9‐yl)phenyl)acridin‐9(10H)‐one (AC‐Ph‐Cz) and 10‐(5‐(9H‐carbazol‐9‐yl)pyridin‐2‐yl)acridin‐9(10H)‐one (AC‐Py‐Cz) were designed and synthesized. These two materials, characterized with highly twisted and rigid structure, good thermal stability, and balanced carrier‐transporting properties, were employed as host materials for green phosphorescent and thermally activated delayed fluorescent organic light‐emitting diodes (OLEDs). The carbazole group, despite its small contribution to the highest occupied molecular orbitals (HOMOs) of these two materials, plays an essential role as an intramolecular host in energy delivering and improving the hole transporting ability of these two hosts. The incorporation of the electron‐deficient pyridyl group as a linking group slightly improves the electron transporting capability of AC‐Py‐Cz. The green phosphorescent OLED (PhOLED) based on AC‐Py‐Cz exhibited excellent device performance with a turn‐on voltage of 2.5 V, a maximum power efficiency and an external quantum efficiency (ηext) of 89.8 lm W−1 and 25.2 %, respectively, benefitting from the better charge‐balancing ability of AC‐Py‐Cz host due to the presence of the pyridyl bridge. More importantly, all the devices based on these two hosts showed low efficiency roll‐off at high brightness due to the suppressed non‐radiative transition in the emitting layer. In particular, the AC‐Py‐Cz‐hosted green PhOLED exhibited an efficiency roll‐off of 1.6 % from the maximum next at a high brightness of 1000 cd m−2 and a roll‐off of 15.9 % at an extremely high brightness of 10000 cd m−2. This study manifests that acridone‐based host materials have great potential in fabricating OLEDs with low efficiency roll‐off. [ABSTRACT FROM AUTHOR]

Acyclic and cyclic acridone‐2,7‐diyl oligomers were synthesized by an iterative procedure from 10‐mesitylacridone as heteroatom containing π‐conjugated compounds. The oligomeric chain was elongated by a combination of regioselective bromination, borylation, Ni(0)‐mediated homocoupling, and Suzuki‐Miyaura coupling up to acyclic hexamer. Subsequently, the cyclic hexamer was synthesized by the bromination and intramolecular coupling of the acyclic hexamer. The DFT calculations revealed that the acyclic oligomers preferred to take extended structures with anti conformations, whereas the cyclic hexamer took a macrocyclic structure with syn conformations. The UV/Vis and fluorescence spectra of the series of oligomers were measured, and the effects of the chain length and the cyclization are discussed in terms of π‐conjugation. [ABSTRACT FROM AUTHOR]

To develop environmentally adapted products, there is a necessity of getting information about the environmental impact of acridone derivatives commonly recognized to possess a variety of biological activities. Acridones are widespread in nature, but the issue related to the acridone series compounds effect on mushrooms still remains practically unstudied. Fungi are a group of living organisms very interesting in theoretical and practical respect. One of the first macrofungi to be cultivated at large scale was the basidiomycete Lentinula edodes (Berk.) Pegler, otherwise known as shiitake. Research into the character of the mode of action of acridone-based substances on various living systems is necessary to elucidate the possible unfavorable biological consequences and to improve measures on their ecological safety. This work reports on the effect of acridone, 1-carboxyacridone, and acridone-N-acetic acid on shiitake mushroom agar culture. Chromato-mass spectrometric analysis was performed in the mode of gas chromatography with mass-selective detection (GC-MS) to follow the decomposition of acridone and its carboxy derivatives by L. edodes culture in solid-state fermentation. The results obtained testify to the relative ecological safety of these substances for mushroom organism, and to the mycelial growth promoting capability of acridone-N-acetic acid at favorable concentrations under these culture conditions. The next step toward the investigation into the systems “macromycete - acridone series compound” has been made.

Acridone as a new kind of visible light photocatalyst has been developed to catalyze metal free atom transfer radical polymerization (ATRP). The photocatalyst possess low excited state potential as can undergo an oxidative quenching pathway to initiate ATRP of vinyl monomers. Kinetic study and light on/off reaction demonstrate the "living"/controlled nature of the polymerization by light. Block copolymers can be achieved by using PMMA as macroinitiator to reinitiate polymerization of other vinyl monomers, which shows highly preserved Br chain‐end functionality in the synthesized polymers. Moreover, the polymerization can be conducted under air atmosphere as most photocatalysts need anaerobic condition, which may give inspiration of further application of this kind of photocatalyst. [ABSTRACT FROM AUTHOR]

An aromatic alkaloid-rich 'absolute' extract from Vepris gossweileri inhibited Saccharomyces cerevisiae at 62.5 μg.mL−1 and Bacillus subtilis at 500 μg.mL−1. A loss of activity upon fractionation indicated possible synergistic effects. Three new acridones, gossweicridone A (3), B (4) and C (5) and known compounds from the extract were inactive. Combinations of compounds showed that a sub-fraction containing mixtures of minor compounds with (Ε)-caryophyllene augmented activity by 50-folds, with MIC values of 19.6 μg.mL−1 for S. cerevisiae and 375.0 μg.mL−1 for B. subtilis, demonstrating potent ΣFIC values of 0.02 and 0.375 respectively. From the active sub-fraction, three compounds were assigned as tecleanatalensine B, 13S-hydroxy-9Z,11E,15E-octadecatrienoic acid and normelicopine. In combination with (Ε)-caryophyllene they separately demonstrated MIC values of 18 μg.mL−1, 34 μg.mL−1 and 16 μg.mL−1, respectively against S. cerevisiae. The synergistic combinations were more potent with addition of pheophytin A, suggesting that the synergistic antifungal effect of the extract is multi-layered. [ABSTRACT FROM AUTHOR]

Several new amino-substituted acridone and xanthone derivatives have been designed and synthesized, using an efficient methodology from suitable acridone- or xanthone-carboxylic acid intermediates. The antiproliferative activity of the target compounds has been evaluated against four cancer cell lines, namely breast adenocarcinoma MCF-7, acute lymphocytic leukemia CCRF-CEM, and its doxorubicin-resistant variant CEM/ADR5000 and prostate cancer PC-3 cell lines. Selected derivatives have also been tested against the urinary bladder T24 and metastatic melanoma WM266-4 cancer cell lines. Two nitro substituted acridones, bearing a basic side chain as well, were endowed with a remarkable profile against the majority of the cell lines tested, with IC50 values in the low micromolar range. Both compounds cause accumulation at G0/G1 phase, induce apoptosis, and act as potent autophagy inhibitors in PC-3 cells, suggesting their further evaluation in various pathophysiological environments, conditions, and regimens.

Novel N-acylhydrazone derivatives from acridone have been synthesized by condensation of acridone acetohydrazide and various aldehyde. The novel acylhydrazones were tested for their in-vitro antibacterial activity against human pathogenic strains. The MIC results indicate that compound 3f displayed high antibacterial potential against Pseudomonas putida with MIC = 38.46 µg/mL, which is very close to that obtained with the commercial antibiotic. The synthesized compounds were subjected for docking studies to understand the interaction of our compounds and transcriptional regulator enzyme of pseudomonas putida and DNA gyrase complex of Staphyloccocus aureus.

Zanthoxylum leprieurii is a medicinal plant widely studied due to its great phytochemical diversity, especially its acrinonic alkaloids, which have shown to be promising anticancer candidates. The aim of this work was to promote the isolation of acridonic alkaloids from fruits of Z. leprieurii and carried out absorption and fluorescence spectroscopy studies with calf thymus DNA and BSA. Five acridone alkaloids have been isolated, including the first description of 3-desmethoxy arborinine ( 2 ). In the study of interaction with biomacromolecules it was observed that all compounds show interaction with calf thymus DNA and BSA. Compound 2 promoted the bigger increase in BSA fluorescence (3.01%) with a lower fluorescence quenching constant (Ksv = 0.13 × 10 4 ). Taken together, these results reaffirm the great phytochemical diversity of Z. leprieurii , and show that acridonic alkaloids have an affinity with both DNA and BSA, therefore providing clues to their mechanisms of action related to their anticancer activities.

N‐substituted acridine‐containing 1,2‐dioxetanes have been recently proposed as thermochemiluminescence (TCL) universal labels for bioanalytical applications. The TCL properties of these compounds markedly depend on the nature of substituents of the acridine ring. In the attempt to obtain new TCL probes with improved properties and stability, the push‐pull approach was adopted, in which both electron withdrawing and electron donating groups are present in the acridine moiety. The results have been useful to better understand the role of the different decorations at the acridine fluorophore in modulating the photophysical properties and the activation parameters of 1,2‐dioxetane labels. Moreover, the great versatility and innovation of these molecules make them extremely attractive for bioanalytical applications, in particular as labels for immune‐ and gene‐probe assays. [ABSTRACT FROM AUTHOR]

Bioactivity-guided fractionation of the CHCl3-soluble extract of the roots of Paramignya trimera was carried out to obtain a new acridone alkaloid, paratrimerin I. Its structure was elucidated based on NMR spectroscopic data interpretation. Paratrimerin I showed noteworthy cytotoxicity against the HepG2 human hepatocellular and MCF-7 human breast carcinoma cell lines, with the submicromolar IC50 values of 0.43 and 0.26 µM, respectively. The N-methyl, C-4 methoxy, and C-5 hydroxy groups in the acridone skeleton can be proposed as a structural feature for good cytotoxicity. [ABSTRACT FROM AUTHOR]

We report the chemistry and biological activities of a Cameroonian Citrus clementina Hort. Ex Tanaka, a vegetatively propagated species. The compounds isolated from this plant were determined to be the known 5-hydroxy-6,7,8,3',4'-pentamethoxyflavone (1), tangerine (3), nobilletin (4), 5,7,8,4'-tetramethoxyflavone (5), citracridone I (6), 5-hydroxynoracronycine (7), citracridone III (8), xanthyletin (10), suberosin (9), E-suberenol (11), E-methoxysuberenol (13), 6-formylumbelliferone (12), aurantiamide acetate (2), limonin (14), stigmasterol, β-sitosterol and β-sitosterol-3-O-β-D-glucoside. The structures of the compounds were established on the basis of their NMR spectroscopic data and comparison with published data. Methanol leaf extract and compounds 1, 2, 4, 6, 7 and 10 were evaluated for their anti-inflammatory, antioxidant, urease and anti-diabetic effects. Compound 10 showed antioxidant activity, anti-inflammatory effect, urease activity and anti-diabetic activity with IC50 values of 47.3 µM, 33.5 µM, 25.2 µM and 33.9 µM respectively, values that were comparable to the respective positive standards. [ABSTRACT FROM AUTHOR]

Abstract Background Acridone alkaloids are heterocyclic compounds that exhibit a broad-range of pharmaceutical and chemotherapeutic activities, including anticancer, antiviral, anti-inflammatory, antimalarial, and antimicrobial effects. Certain plant species such as Citrus microcarpa, Ruta graveolens, and Toddaliopsis bremekampii synthesize acridone alkaloids from anthranilate and malonyl-CoA. Results We synthesized two acridones in Escherichia coli. Acridone synthase (ACS) and anthraniloyl-CoA ligase genes were transformed into E. coli, and the synthesis of acridone was examined. To increase the levels of endogenous anthranilate, we tested several constructs expressing proteins involved in the shikimate pathway and selected the best construct. To boost the supply of malonyl-CoA, genes coding for acetyl-coenzyme A carboxylase (ACC) from Photorhabdus luminescens were overexpressed in E. coli. For the synthesis of 1,3-dihydroxy-10-methylacridone, we utilized an N-methyltransferase gene (NMT) to supply N-methylanthranilate and a new N-methylanthraniloyl-CoA ligase. After selecting the best combination of genes, approximately 17.3 mg/L of 1,3-dihydroxy-9(10H)-acridone (DHA) and 26.0 mg/L of 1,3-dihydroxy-10-methylacridone (NMA) were synthesized. Conclusions Two bioactive acridone derivatives were synthesized by expressing type III plant polyketide synthases and other genes in E. coli, which increased the supplement of substrates. This study showed that is possible to synthesize diverse polyketides in E. coli using plant polyketide synthases.

A series of new acridone derivatives from isoxazoline (2a-l) were synthesized via 1,3-dipolar cycloaddition reaction between a variety of aryl nitrile oxides and N-allyl acridones using simple and efficient methods. This is the first ever green protocol to synthesize novel isoxazolines derivatives from acridone under microwave condition and offers broad substrate scope with good to excellent yields. The synthesized compounds (2a-l) were tested for their antibacterial potency against four pathogenic bacterial and were found to exhibit moderate to potent antibacterial activity. Two of these compounds 2a and 2k exhibited a significant antibacterial activity against E. coli and P. putida, respectively. The in silico molecular docking results supported the antibacterial activity of the synthesized compounds. ADMET properties of the most synthetized compounds showed an excellent bioavailability, therefore, can be considered as promising drugs candidates for further studies.

To develop environmentally adapted products, there is a necessity of getting information about the environmental impact of acridone derivatives commonly recognized to possess a variety of biological activities. Acridones are widespread in nature, but the issue related to the acridone series compounds effect on mushrooms still remains practically unstudied. Fungi are a group of living organisms very interesting in theoretical and practical respect. One of the first macrofungi to be cultivated at large scale was the basidiomycete Lentinula edodes (Berk.) Pegler, otherwise known as shiitake. Research into the character of the mode of action of acridone-based substances on various living systems is necessary to elucidate the possible unfavorable biological consequences and to improve measures on their ecological safety. This work reports on the effect of acridone, 1-carboxyacridone, and acridone-N-acetic acid on shiitake mushroom agar culture. Chromato-mass spectrometric analysis was performed in the mode of gas chromatography with mass-selective detection (GC-MS) to follow the decomposition of acridone and its carboxy derivatives by L. edodes culture in solid-state fermentation. The results obtained testify to the relative ecological safety of these substances for mushroom organism, and to the mycelial growth promoting capability of acridone-N-acetic acid at favorable concentrations under these culture conditions. The next step toward the investigation into the systems "macromycete - acridone series compound" has been made. [ABSTRACT FROM AUTHOR]

Fluorescent amino acids are powerful biophysical tools as they can be used in structural or imaging studies of a given protein without significantly perturbing its native fold or function. Here, we have synthesized and characterized 7-(dimethylamino)acridon-2-ylalanine (Dad), a red-shifted derivative of the geneticallyincorporable amino acid, acridon-2-ylalanine. Alkylation increases the quantum yield and fluorescence lifetime of Dad relative to a previously published amino acid, 7-aminoacridon-2-ylalanine (Aad). These properties of Dad make it a potentially valuable protein label, and we have performed initial testing of its ability to be genetically incorporated using an evolved aminoacyl tRNA synthetase. [ABSTRACT FROM AUTHOR]

Two series of eight visible‐light‐absorbing redox active molecules derived from 9(10H)‐acridone and thioxanthen‐9‐one were designed and synthetized. The different dyes were characterized by UV‐vis absorption and fluorescent spectroscopy, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and cyclic voltammetry (CV) for their thermal, optical and electrochemical properties, respectively. Theoretical calculations DFT were also carried out to support the experimental results. These molecules are thermally stable with Td (decomposition temperature) range from 290 °C to 418 °C and have glass forming properties with Tg (glass transition temperature) varying from 44 °C to 134 °C. These chromophores strongly absorb and emit in the visible spectral range (400–550 nm for absorption and 450–650 for fluorescence). Their frontier orbitals' energy levels as well as optical bandgaps can be tuned by changing the nature and the number of the arylamine electron‐donating groups. These compounds have been found to be promising candidates for photo‐initiators for photo‐polymerization process applied in 3D printing technique. They could also be potentially applied as hole transporting materials for hybrid perovskite photovoltaics. [ABSTRACT FROM AUTHOR]

Tricyclic acridone derivatives have been extensively developed as antimicrobial, antimalarial, and antitumor drugs due to their broad spectrum of drug design and biological activity. In this study, we developed a surfactant-like acridone scaffold that contained two vinylpyridines and a dodecyl pyridine chain. The acridone scaffold decorated the dodecyl pyridine chain by N-bromosuccinimide reagent. The surfactant-like core scaffold incorporated with 4-vinylpyridines at the 2- and 7-positions via a Heck coupling reaction. Subsequently, the acridone derivatives were methylated onto these pyridine groups. Here we developed two similar acridone derivatives, MedAcd12C and MedAcd12P. The MedAcd12C incorporated two pyridine groups, and MedAcd12P incorporated three pyridine groups. MedAcd12C and MedAcd12P have two identical vinylpyridines and the different anchor tails at the N10 position. Their physicochemical properties, cell compatibility, and photoluminescence were demonstrated. Although both compounds have no fluorescence emission in water solution, MedAcd12P and MedAcd12C significantly appeared with orange light emission in the cellular imaging. We suggested that the surfactant-like scaffold promoted the drugs' self-assembly and caused the aggregation-induced emission (AIE) after cellular uptake. This innovative design endowed acridone derivatives with an AIE and traceability for cell imaging. [ABSTRACT FROM AUTHOR]

Several new amino-substituted acridone and xanthone derivatives have been designed and synthesized, using an efficient methodology from suitable acridone- or xanthone-carboxylic acid intermediates. The antiproliferative activity of the target compounds has been evaluated against four cancer cell lines, namely breast adenocarcinoma MCF-7, acute lymphocytic leukemia CCRF-CEM, and its doxorubicin-resistant variant CEM/ADR5000 and prostate cancer PC-3 cell lines. Selected derivatives have also been tested against the urinary bladder T24 and metastatic melanoma WM266-4 cancer cell lines. Two nitro substituted acridones, bearing a basic side chain as well, were endowed with a remarkable profile against the majority of the cell lines tested, with IC 50 values in the low micromolar range. Both compounds cause accumulation at G0/G1 phase, induce apoptosis, and act as potent autophagy inhibitors in PC-3 cells, suggesting their further evaluation in various pathophysiological environments, conditions, and regimens. [ABSTRACT FROM AUTHOR]

Benzene‐ and naphthalene‐fused acridone derivatives with hexyl and phenyl groups at the amino position were synthesized and their properties were investigated experimentally and computationally. All the structures of these fused π‐extended acridone derivatives were unambiguously confirmed by single‐crystal X‐ray analysis, which revealed the presence of face‐to‐face π–π stackings along the acridone moiety and the intermolecular hydrogen bond‐directed molecular packings of the phenyl‐substituted acridone derivatives in the crystals. Moreover, the dimerization of linearly fused acridone derivative was observed after storing the crystals over months. The benzene ring at the turning point of the angularly fused acridone derivatives contained relatively longer and shorter C–C bonds, which affected the molecular conjugation, as confirmed by the results of photophysical characterization and the study of the aromaticity. Mobility calculations based on the molecular packings in the single crystals showed that the linearly fused acridone derivatives bearing better electron and hole mobilities are good candidates of organic functional materials. [ABSTRACT FROM AUTHOR]

Development of new drugs with antibacterial potency is an important solution to overcome drug-resistance problems. In the goal to develop novel structure with antibacterial potency, we designed and synthesized novel acridone derivatives bearing triazole nucleus. The novel synthesized compounds were tested for their in vitro antibacterial activity against four bacterial human pathogenic strains. The compound 4h displayed significant antibacterial activities against Staphylcoccus aureus (MRSA) with MIC = 19.6 μg/mL. The synthesized compounds were subjected for docking study to understand the interaction of our compounds and the dihydropteroate synthase (DHPS) in methicillin-resistant Staphylcoccus aureus (MRSA). [ABSTRACT FROM AUTHOR]

Acridine-based compounds possess anticancer activities by intercalating to DNA. Although they have chemotherapeutic potential, acridine-based compounds are not used to treat cancer. In this study, 2, N 10-acridone derivatives are designed and synthesized based on acridone, a ketone derivative of acridine. Herein, acridone is functionalized with alkyl side chains containing terminal nitrogen-based moieties at the N 10-position and substituted at the C2-position. The products are evaluated for in vitro cytotoxicity against four cancer cell lines: Molt-3, HepG2, A549, and HuCCA-1. The derivative bearing two butyl piperidine side chains at the C2- and N 10-positions is the most active, with IC50 values ranging from 2.96 to 9.46 µM. Molecular modeling studies supported the binding of the derivatives to DNA by intercalation, thereby confirming the observed cytotoxic effects. [ABSTRACT FROM AUTHOR]

Novel N-acylhydrazone derivatives from acridone have been synthesized by condensation of acridone acetohydrazide and various aldehyde. The novel acylhydrazones were tested for their in-vitro antibacterial activity against human pathogenic strains. The MIC results indicate that compound 3f displayed high antibacterial potential against Pseudomonas putida with MIC = 38.46 µg/mL, which is very close to that obtained with the commercial antibiotic. The synthesized compounds were subjected for docking studies to understand the interaction of our compounds and transcriptional regulator enzyme of pseudomonas putida and DNA gyrase complex of Staphyloccocus aureus. [ABSTRACT FROM AUTHOR]

The surface extension of all‐carbon based bowl‐shaped molecules, such as corannulene and sumanene, to synthesize even larger buckybowls has been widely studied, leaving other concave compounds with heteroatoms less considered. Herein we present a highly curved molecule synthesized via stepwise cyclization of fjords of a bisacridone derivative. Crystallographic analysis unambiguously confirmed a boat‐shaped structure with deformed bottom benzene ring. Theoretical calculation unravels an inversion process with an S‐shaped transition structure rather than a planar one. The enlarged boat demonstrates interesting properties, such as red shifts in absorption and emission spectra, enhanced emission intensity, and convergent frontier molecular orbital energy levels, in comparison to the related concave N‐heterotriangulene. [ABSTRACT FROM AUTHOR]

Background: Acridone alkaloids are heterocyclic compounds that exhibit a broad-range of pharmaceutical and chemotherapeutic activities, including anticancer, antiviral, anti-inflammatory, antimalarial, and antimicrobial effects. Certain plant species such as Citrus microcarpa, Ruta graveolens, and Toddaliopsis bremekampii synthesize acridone alkaloids from anthranilate and malonyl-CoA. Results: We synthesized two acridones in Escherichia coli. Acridone synthase (ACS) and anthraniloyl-CoA ligase genes were transformed into E. coli, and the synthesis of acridone was examined. To increase the levels of endogenous anthranilate, we tested several constructs expressing proteins involved in the shikimate pathway and selected the best construct. To boost the supply of malonyl-CoA, genes coding for acetyl-coenzyme A carboxylase (ACC) from Photorhabdus luminescens were overexpressed in E. coli. For the synthesis of 1,3-dihydroxy-10-methylacridone, we utilized an N-methyltransferase gene (NMT) to supply N-methylanthranilate and a new N-methylanthraniloyl-CoA ligase. After selecting the best combination of genes, approximately 17.3 mg/L of 1,3-dihydroxy-9(10H)-acridone (DHA) and 26.0 mg/L of 1,3-dihydroxy-10-methylacridone (NMA) were synthesized. Conclusions: Two bioactive acridone derivatives were synthesized by expressing type III plant polyketide synthases and other genes in E. coli, which increased the supplement of substrates. This study showed that is possible to synthesize diverse polyketides in E. coli using plant polyketide synthases. [ABSTRACT FROM AUTHOR]

This study describes the synthesis of an acridone through the directed lithiation of a diarylamine, and elaboration via the 4,5‐dibromoacridone. The bromo substituents are amenable to Suzuki‐Miyaura coupling. Conversion to a 9‐chloro‐4,5‐dibromoacridine, followed by bromine‐lithium exchange, allows the preparation of a 4,5‐bis (phosphino)‐9‐chloroacridine. The 9‐chloro moiety undergoes nucleophilic aromatic substitution by methoxide or an aryloxide. One‐electron reduction of a 9‐(aryloxy)‐4,5‐bis(phosphino)acridine affords a stable radical anion. [ABSTRACT FROM AUTHOR]

Evaluating the binding interaction between biomacromolecules and various chemical compounds is one of the most biologically researched topics. The present experimental study attempted to investigate the binding interaction between two types of acridone derivative, namely 8-chloro acridone (CA) and nitrile cyanide acridone (NCA) as antineoplastic agents and calf thymus DNA (ctDNA) by applying various spectroscopic techniques. The binding interactions were first characterized by fluorescence quenching experiments, and it was demonstrated that NCA had higher affinity to ctDNA and bound to it more tightly. Further analysis indicated that the quenching process between CA and ctDNA was controlled by a dynamic mechanism, while the dominant process in ctDNA–NCA interaction was static. Analysis of thermodynamic parameters showed that hydrophobic forces played a key role in the interaction between ctDNA and CA, whereas ctDNA–NCA complex was mainly stabilized by van der Waals interactions. In terms of the latter interaction, external binding also contributed to the stabilization of the formed complex. On the basis of RLS results, we concluded that CA had stronger potential toxicity on ctDNA than NCA. Fluorescence competition studies aimed at uncovering the mode of binding and indicated that CA and NCA probably intercalated into ctDNA. Thermal denaturation studies confirmed the displacement experiments and showed that CA brought about a stronger effect on the ctDNA stabilization. Data gathered by spectroscopy studies were further supported by viscosity experiments. These studies also showed that CA and NCA intercalated into ctDNA by a non-classical and classical mode, respectively. The results of circular dichroism experiments revealed no considerable conformational transition occurred in ctDNA upon the binding interactions and ctDNA remained in B-form. Based on the spectroscopic results and the binding affinity of CA to double-strand and single-strand ctDNA, we inferred that although CA predominantly intercalated into ctDNA, a small population of its molecules might bind to the grooves of ctDNA. In case of NCA, all the experimental results confirmed that NCA molecules intercalated into ctDNA by a classical mode. [ABSTRACT FROM AUTHOR]

Acridone‐functionalized carbazole dendrimers were synthesized via copper‐catalyzed Ullmann amination and their properties were investigated by spectroscopic and electrochemical measurements, as well as theoretical calculations. The results reveal that the properties of the carbazole dendrimers vary according to the position of acridone. Intramolecular charge transfer between the acridone core and the outer carbazole dendron is observed, accompanying a red shift of the emission maximum and a decline of quantum yields with the rise of the dendrimer generation. Whereas the internal carbazole unit has little influences on the photoluminescence of dendrimers with acridone at the periphery in solution. The electrochemical analysis and theoretical calculations demonstrate a convergence in HOMO and LUMO energy levels in dendrimers bearing the acridone core and a decrease in both of these energy levels in dendrimers with the acridone at the periphery when the dendrimer generation increases. [ABSTRACT FROM AUTHOR]

A variety of N‐substituted acridone derivatives were synthesized to make a comparison of their properties according to the number of acridone unit and the nature of substituent. The spectroscopic and electrochemical investigations show that the properties of N‐substituted acridone derivatives are substituent‐dependent. With benzene, biphenyl, fluorene and carbazole as linkers, the acridone derivatives demonstrate the properties of acridone itself due to a very weak intramolecular charge transfer (ICT) between acridone and the linker. However, significant ICT process is observed when the electron withdrawing groups are involved to form the donor–acceptor systems with acridone as the electron donating groups, which is different from the previously reported results of which acridone is usually used as an electron acceptor. Moreover, thermally activated delayed fluorescence (TADF) is observed with anthraquinone as linker. The theoretical calculations reveal that the N‐substitutions have more influences on the locations and energy levels of the LUMOs than those of the HOMOs. [ABSTRACT FROM AUTHOR]

Length‐defined 2,7‐acridone oligomers were synthesized via a sequence of bromination, borylation and Suzuki–Miyaura cross‐coupling reaction. Both the single crystal structure analysis and the theoretical calculations demonstrate that the anti conformation is favored in the oligomer. The relationship of the properties and the number of acridone units in the oligomer was investigated. The UV/Vis absorption and fluorescence spectroscopy reveal that the absorption and emission of oligomers are red‐shifted and energy gaps narrow with the increase of acridone moieties, as well as a decline in the radiative decay rate. Cyclic voltammetry measurements and theoretical calculations elucidate that the quantity of acridone in the oligomer plays a greater effect on the HOMO energy levels than on the LUMO ones. [ABSTRACT FROM AUTHOR]

Tricyclic acridone derivatives have been extensively developed as antimicrobial, antimalarial, and antitumor drugs due to their broad spectrum of drug design and biological activity. In this study, we developed a surfactant-like acridone scaffold that contained two vinylpyridines and a dodecyl pyridine chain. The acridone scaffold decorated the dodecyl pyridine chain by N-bromosuccinimide reagent. The surfactant-like core scaffold incorporated with 4-vinylpyridines at the 2- and 7-positions via a Heck coupling reaction. Subsequently, the acridone derivatives were methylated onto these pyridine groups. Here we developed two similar acridone derivatives, MedAcd12C and MedAcd12P. The MedAcd12C incorporated two pyridine groups, and MedAcd12P incorporated three pyridine groups. MedAcd12C and MedAcd12P have two identical vinylpyridines and the different anchor tails at the N10 position. Their physicochemical properties, cell compatibility, and photoluminescence were demonstrated. Although both compounds have no fluorescence emission in water solution, MedAcd12P and MedAcd12C significantly appeared with orange light emission in the cellular imaging. We suggested that the surfactant-like scaffold promoted the drugs’ self-assembly and caused the aggregation-induced emission (AIE) after cellular uptake. This innovative design endowed acridone derivatives with an AIE and traceability for cell imaging.

The N-functionalized amino acid N-methylanthranilate is an important precursor for bioactive compounds such as anticancer acridone alkaloids, the antinociceptive alkaloid O-isopropyl N-methylanthranilate, the flavor compound O-methyl-N-methylanthranilate, and as a building block for peptide-based drugs. Current chemical and biocatalytic synthetic routes to N-alkylated amino acids are often unprofitable and restricted to low yields or high costs through cofactor regeneration systems. Amino acid fermentation processes using the Gram-positive bacterium Corynebacterium glutamicum are operated industrially at the million tons per annum scale. Fermentative processes using C. glutamicum for N-alkylated amino acids based on an imine reductase have been developed, while N-alkylation of the aromatic amino acid anthranilate with S-adenosyl methionine as methyl-donor has not been described for this bacterium. After metabolic engineering for enhanced supply of anthranilate by channeling carbon flux into the shikimate pathway, preventing by-product formation and enhancing sugar uptake, heterologous expression of the gene anmt encoding anthranilate N-methyltransferase from Ruta graveolens resulted in production of N-methylanthranilate (NMA), which accumulated in the culture medium. Increased SAM regeneration by coexpression of the homologous adenosylhomocysteinase gene sahH improved N-methylanthranilate production. In a test bioreactor culture, the metabolically engineered C. glutamicum C1* strain produced NMA to a final titer of 0.5 g·L−1 with a volumetric productivity of 0.01 g·L−1·h−1 and a yield of 4.8 mg·g−1 glucose.

Acridone, a cyclic analogue of benzophenone that undergoes efficient intersystem crossing (ISC) to the triplet-excited state with near-unity quantum yield, was elaborated as a 3-connecting triacid linker, i.e., H 3 AcTA , with a solvent-accessible volume of ca. 31%. The protection of the acridone chromophore in the MOF in conjunction with a wider cross-section of its absorption in the visible region renders the MOF an excellent heterogeneous photosensitizer for singlet oxygen ( 2+ )-assisted self-assembly of the triacid yielded a Zn-MOF, i.e., Zn-AcTA , with a solvent-accessible volume of ca. 31%. The protection of the acridone chromophore in the MOF in conjunction with a wider cross-section of its absorption in the visible region renders the MOF an excellent heterogeneous photosensitizer for singlet oxygen ( 1 O 2 ) generation by energy transfer to the ground-state triplet oxygen ( 3 O 2 is established as the reactive oxygen species in photocatalytic oxidation reactions. The results constitute the first demonstration of rational development of a photocatalytic MOF based on acridone for heterogeneous oxidations mediated by 1 O 2 is established as the reactive oxygen species in photocatalytic oxidation reactions. The results constitute the first demonstration of rational development of a photocatalytic MOF based on acridone for heterogeneous oxidations mediated by 1 O 2 .

We separated and structurally elucidated three new acridone alkaloids (glycomontamine A ( 1 ), B ( 2 ), and C ( 3 )), together with three known compounds (glycofoline, kokusaginine and dictamnine) from the acetone extract of Glycosmis lanceolata (Blume) D.Dietr. branches collected in Thailand. The compounds were assayed for cell viability using human lung adenocarcinoma cell line A549, breast adenocarcinoma cell line T47D, cervix epithelioid carcinoma cell line Hela, acute lymphoid leukaemia B cell line NALM-6, and human dermal fibroblasts. The viability of Hela cells treated with compound 1 (IC 50 17.6 μM) and T47D cells treated with compound 2 (IC 50 17.4 μM) decreased dose-dependently. Both compounds also showed cytotoxicity against NALM-6 cells (IC 50 16.5 and 9.3 μM). Additionally, compound 1 decreased the mitochondrial membrane potential of Hela cells, whereas compound 2 did not change the mitochondrial membrane potential in T47D cells.