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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]

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]

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.

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]

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.

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]

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]

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.

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]

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.

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.

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]

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]

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]

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.

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., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mauricio Lacerda Nogueira reports financial support was provided by The Coordinating Research on Emerging Arboviral Threats Encompassing the Neotropics., (© 2023 The Author(s).)

[Display omitted] • Various acridone derivatives were synthesized and evaluated for anticancer activity. • C4 exhibited potent activity against Hep-G2 cells with IC 50 value of 6.29 ± 0.93 μM. • C4 could specifically bind to and destabilize Kras gene promoter i-motif structure. • C4 down-regulated Kras gene expression possibly through its promoter i-motif. • C4 induced cell apoptosis possibly related to its effect on mitochondrial dysfunction. Two series of novel acridone derivatives were designed and synthesized, with their anticancer activity evaluated. Most of these compounds showed potent antiproliferative activity against cancer cell lines. Among them, compound C4 with dual 1,2,3-triazol moieties exhibited the most potent activity against Hep-G2 cells with IC 50 value determined to be 6.29 ± 0.93 μM. Subsequent experiments showed that C4 could bind to and destabilize Kras gene promoter i-motif structure without significant interaction with its corresponding G-quadruplex. C4 could down-regulate Kras expression in Hep-G2 cells, possibly due to its interaction with the Kras i-motif. Further cellular studies indicated that C4 could induce apoptosis of Hep-G2 cells, possibly related to its effect on mitochondrial dysfunction. These results indicated that C4 could be further developed as a promising anticancer agent. [ABSTRACT FROM AUTHOR]

Synthesis of acridine derivatives that act as DNA-targeting anticancer agents is an evolving field and has resulted in the introduction of several drugs into clinical trials. Carboranes can be of importance in designing biologically active compounds due to their specific properties. Therefore, a series of novel acridine analogs modified with carborane clusters were synthesized. The DNA-binding ability of these analogs was evaluated on calf thymus DNA (ct-DNA). Results of these analyses showed that 9-[(1,7-dicarba-closo-dodecaborane-1-yl)propylamino]acridine (30) interacted strongly with ct-DNA, indicating its ability to intercalate into DNA, whereas 9-[(1,7-dicarba-closo-dodecaborane-1-yl)propanamido]acridine (29) changed the B-form of ct-DNA to the Z form. Compound 30 demonstrated cytotoxicity, was able to inhibit cell proliferation, arrest the cell cycle in the S phase in the HeLa cancer cell line, and induced the production of reactive oxygen species (ROS). In addition, it was specifically localized in lysosomes and was a weak inhibitor of Topo IIα., (© 2023 Wiley-VCH GmbH.)

Seven undescribed compounds, including four acridones, two coumarins, and a phenylpropanoid, together with 13 known acridone analogues were isolated from the ethanolic extract of the stems and leaves of Glycosmis ovoidea Pierre. Their structures were elucidated on the basis of comprehensive analysis of 1D and 2D NMR and HRESIMS spectroscopic data, and the absolute configurations were assigned by comparison of the experimental and calculated ECD data. Five compounds showed moderate inhibitory effects on nitric oxide production stimulated by lipopolysaccharide in BV-2 microglial cells with IC 50 values in the range of 18.30–30.84 μM, and three compounds showed potent inhibition on 5-lipoxygenase (5-LOX) with IC 50 values in the range of 2.08–10.26 μM. The possible binding sites of the active compounds with 5-LOX were further performed by molecular docking. [Display omitted] • Twenty compounds were isolated from Glycosmis ovoidea Pierre. • Four acridones, two coumarins, and a phenylpropanoid were first obtained. • Five compounds showed moderate inhibitory effects on NO production stimulated by LPS. • Three compounds showed potent inhibition on 5-LOX. [ABSTRACT FROM AUTHOR]

• Four novel acridone derivatives are synthesized and subjected to the X-ray crystallography and DFT studies to comprehend the structural assemblies of these derivatives. • Hirsfeld surface and 2D-Finger plot analyzes were supported the crystal packing. • Comparable computational and experimental results attained using DFT/B3LYP/6–311++G (d,p) and X-ray crystal analysis, respectively. • The electrostatic Potentials (ESP) analysis was used to visualize the charge distribution on the molecule. [Display omitted] The title compounds include an acridone as a parent molecule in which nitrogen is linked to other nitrogen-containing heterocyclic molecules through two carbon chain alkyl linkers connected by a C—N single bond. These acridone derivatives crystallized as Triclinic, Monoclinic, Tetragonal, and Orthorhombic having space group P 1, P 2 1 / c, I 4 1 / a, Pca 2 1 , respectively at T = 273 K. In the present work, synthesis and single-crystal X-ray crystallographic study of four novel acridone derivatives are reported from the perspective of crystal engineering. This work is based on the comprehensive analysis of Hirshfeld surfaces, 2D fingerprint plots, and DFT studies. The single-crystal structure analysis showed that compounds are connected by various intermolecular interactions such as C – H⋯O, C – H⋯C/π, and π⋯π (C⋯C) stacking interactions, which are accountable for the arrangement and amplification of molecular assembly. The DFT studies using the B3LYP functional with the 6-311++ G (d,p) basis set are employed to compare the experimental results with theoretically obtained molecular parameters. The HOMO and LUMO analyzes were used to elucidate information regarding molecular reactivity and charge transfer within the molecule. [ABSTRACT FROM AUTHOR]

Type III polyketide synthases (PKSs) catalyze sequential condensations of acyl-CoA thioesters to generate a variety of polyketide scaffolds with remarkable structural diversity and significant biological activities. These enzymes share a similar thiolase fold and use a common catalytic triad for the polyketide chain elongation and cyclization reactions. Structural and biochemical analyses of type III PKSs revealed that the functional diversity of these highly homologous enzymes is attributable to subtle changes in their active site volumes and architectures. The accumulated knowledge of their detailed catalytic versatility and mechanisms provides a platform for enzyme engineering via structure-guided approaches for the generation of unnatural novel polyketides. In this chapter, the methods for identification, biochemical characterization, and structure-guided engineering of polyketide synthases will be described in detail, along with brief overviews of the structures and functions of these enzymes., (Copyright © 2022 Elsevier Inc. All rights reserved.)