Search Results (58)

Commercial herbal compounds are a main attractive target to explore for a novel drug for the treatment of HSV. This study investigated the anti-HSV infectivity of extracts derived from the Thai commercial herbals Kerra^TM, KS^TM, and Minoza^TM. Wild-type HSV-1 KOS, HSV-2, and drug-resistant HSV-1 dxpIII were used to investigate any inhibitory effects of these extracts. A plaque formation assay was performed to investigate the effects of all extracts. The viral ICP4, UL30, gD, and gB and cellular IL1β, IL6, STAT3, and NFKB1 expression levels were evaluated. The Kerra^TM, KS^TM, and Minoza^TM extracts at 50–200 μg/mL significantly inhibited HSV-1 KOS and dxpIII infection in the post-entry step, whereas only Minoza^TM could not reduce plaque formation of HSV-2. In addition, ICP4, UL30, and gD mRNAs and gB protein were significantly decreased in Kerra^TM- and KS^TM-treated cells. Furthermore, IL1B, IL6, STAT3, and NFKB1 expression was upregulated in Kerra^TM- and KS^TM-treated cells. Kerra^TM and KS^TM could be agents against HSV infection, especially the HSV acyclovir (ACV)-resistant strain. From the docking result and drug-likeness prediction, 2-Methoxy-9H-xanthen-9-one, piperine, and sargassopenilline D found in Kerra^TM, KS^TM, and Minoza^TM show high binding energy closely resembling ACV, and are desirable as drug-like characteristics. Full article

Rosamines represent one of the most promising groups of xanthene dyes. Their excellent photophysical properties allow their widespread application. Their use as photosensitizers in photodynamic therapy has recently gained considerable attention. Here, we report the facile, effective, microwave-assisted synthesis of rosamine dyes. Pyridylbenzaldehyde derivatives were reacted with 1,3-dialkylaminophenols or 8-hydroxyjulolidine in toluene without any additive. The resulting pyridyl rosamines were investigated for their cytotoxic effect against the A431 human epidermoid carcinoma cell line to estimate their potential as photosensitizers. The compounds displayed light-induced toxicity in the submicromolar or occasionally in the low nanomolar range. One of the julolidine-based derivatives exhibited a phototoxic index above 100, indicating an increase in light-induced cytotoxic efficacy of two orders of magnitude compared to its negligible dark toxicity. This compound is a particularly promising candidate for the development of novel pyridyl-rosamine-based photosensitizers for photodynamic therapy of skin cancer. Full article

Although COVID-19 is not a pandemic anymore, the virus frequently mutates, resulting in new strains and presenting global public health challenges. The lack of oral antiviral drugs makes it difficult to treat him, which makes the creation of broadly acting antivirals necessary to fight current and next epidemics of viruses. Using the molecular docking approach, 118 compounds derived from marine organisms and 92 previously synthesized compounds were screened to assess their binding affinity for the main protease and papain-like protease enzymes of SARS-CoV-2. The best candidates from the xanthene, benzoxazole, and coumarin classes were identified. Marine-derived compounds showed slightly better potential as enzyme inhibitors, though the binding affinities of synthesized compounds were similar, with the best candidates displaying affinity values between 0.2 and 0.4 mM. Xanthenes, among both marine origin and synthesized compounds, emerged as the most promising scaffolds for further research as inhibitors. The papain-like protease was found to be more druggable than the main protease. Additionally, all top candidates met the criteria for various drug-likeness properties, indicating good oral bioavailability and low risk of adverse effects. This research provides valuable insights into the comparative affinities of marine origin and synthesized compounds from the xanthene, coumarin, and benzoxazole classes, highlighting promising candidates for further in vitro and in vivo studies. Full article

The growth of the environment depends upon developing greener and ecological methods for managing pollutants and contamination from industrial wastewater, which causes significant effects on human health. The removal of these pollutants from wastewater using nanomaterials covers an ecological method that is free from expensive and secondary pollution. In this report, we developed magnetic iron nanoparticles from Chenopodium glaucum (CG), which showed excellent adsorption capacity at pH 5 for selective Hg²⁺ and Pb²⁺ metal ions among various heavy metal ions, with maximum adsorption capacities of 96.9 and 94.1%, respectively. These metals’ adsorption process conforms to the Langmuir model, which suggests that monolayer adsorption transpires on CG–Fe₂O₃ nanoparticles. CG–Fe₂O₃ nanoparticles also act as an efficient and recyclable heterogeneous catalyst for one-pot synthesis of xanthene derivatives, yielding products with high yields (up to 97%) and excellent purity (crystalline form) within a short timeframe (6 min) using microwave irradiations (at 120 W). Full article

Global health faces a significant issue with the rise of infectious diseases caused by bacteria, fungi, viruses, and parasites. The increasing number of multi-drug resistant microbial pathogens severely threatens public health worldwide. Antibiotic-resistant pathogenic bacteria, in particular, present a significant challenge. Therefore, there is an urgent need to identify new potential antimicrobial targets and discover new chemical entities that can potentially reverse bacterial resistance. The main goal of this research work was to create and develop a library of 3,6-disubstituted xanthones based on twin drugs and molecular extension approaches to inhibit the activity of efflux pumps. The process involved synthesizing 3,6-diaminoxanthones through the reaction of 9-oxo-9H-xanthene-3,6-diyl bis(trifluoromethanesulfonate) with various primary and secondary amines. The resulting 3,6-disubstituted xanthone derivatives were then tested for their in vitro antimicrobial properties against a range of pathogenic strains and their efficacy in inhibiting the activity of efflux pumps, biofilm formation, and quorum-sensing. Several compounds have exhibited effective antibacterial properties against the Gram-positive bacterial species tested. Xanthone 16, in particular, has demonstrated exceptional efficacy with a remarkable MIC of 11 µM (4 µg/mL) against reference strains Staphylococcus aureus ATCC 25923 and Enterococcus faecalis ATCC 29212, and 25 µM (9 µg/mL) against methicillin-resistant S. aureus 272123. Furthermore, some derivatives have shown potential as antibiofilm agents in a crystal violet assay. The ethidium bromide accumulation assay pinpointed certain compounds inhibiting bacterial efflux pumps. The cytotoxic effect of the most promising compounds was examined in mouse fibroblast cell line NIH/3T3, and two monoamine substituted xanthone derivatives with a hydroxyl substituent did not exhibit any cytotoxicity. Overall, the nature of the substituent was critical in determining the antimicrobial spectra of aminated xanthones. Full article

Colorless and transparent polyimide (CPI) films with good atomic oxygen (AO) resistance and high thermal endurance are highly required in low earth orbit (LEO) space exploration. Conventional CPI films based on fluoro-containing 4,4′-(hexafluoroisopropylidene)diphthalic anhydride (6FDA) have been widely used in space applications. However, the AO erosion yields and glass transition temperatures (T_g) of the 6FDA-based CPI films have to be modified in order to meet the severe serving environments. In the current work, novel CPI films based on a multi-ring fluoro-containing 9,9-bis(trifluoromethyl)xanthene-2,3,6,7-tetracarboxylicdianhydride (6FCDA) monomer were developed. In order to enhance the AO resistance of the derived CPI film, a phosphorus-containing aromatic diamine, 2,5-bis[(4-aminophenoxy)phenyl]diphenylphosphine oxide (BADPO) was used to polymerize with the dianhydride to create the organo-soluble resin. Then, two phosphorus-containing CPI films (PPI), including PPI-1 (6FDA-BADPO) and PPI-2 (6FCDA-BADPO) were prepared by thermally curing of the PPI solutions at elevated temperatures. The PPI films maintained good optical transparency with transmittance values over 80% at a wavelength of 450 nm. PPI-2 exhibited a T_g value of 311.0 °C by differential scanning calorimetry (DSC) measurement, which was 46.7 °C higher than that of the PPI-1 counterpart (T_g = 264.3 °C). In addition, the PPI-2 film showed a coefficient of linear thermal expansion (CTE) value of 41.7 × 10⁻⁶/K in the range of 50~250 °C, which was apparently lower than that of the PPI-1 sample (CTE = 49.2 × 10⁻⁶/K). Lastly, both of the two PPI films exhibited good AO resistance with the erosion yields (E_y) of 6.99 × 10⁻²⁵ cm³/atom for PPI-1 and 7.23 × 10⁻²⁵ cm³/atom for PPI-2 at an exposure flux of 5.0 × 10²⁰ atoms/cm². The E_y values of the current PPI films were obviously lower than that of the standard polyimide (PI) film based on pyromellitic dianhydride (PMDA) and 4,4′-oxydianiline (ODA) (E_y = 3.0 × 10⁻²⁴ cm³/atom). Full article

The spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) relies on host cell surface glycans to facilitate interaction with the angiotensin-converting enzyme 2 (ACE-2) receptor. This interaction between ACE2 and the spike protein is a gateway for the virus to enter host cells and may be targeted by antiviral drugs to inhibit viral infection. Therefore, targeting the interaction between these two proteins is an interesting strategy to prevent SARS-CoV-2 infection. A library of glycan mimetics and derivatives was selected for a virtual screening performed against both ACE2 and spike proteins. Subsequently, in vitro assays were performed on eleven of the most promising in silico compounds to evaluate: (i) their efficacy in inhibiting cell infection by SARS-CoV-2 (using the Vero CCL-81 cell line as a model), (ii) their impact on ACE2 expression (in the Vero CCL-81 and MDA-MB-231 cell lines), and (iii) their cytotoxicity in a human lung cell line (A549). We identified five synthetic compounds with the potential to block SARS-CoV-2 infection, three of them without relevant toxicity in human lung cells. Xanthene 1 stood out as the most promising anti-SARS-CoV-2 agent, inhibiting viral infection and viral replication in Vero CCL-81 cells, without causing cytotoxicity to human lung cells. Full article

The increased proliferation and activation of hepatic stellate cells (HSCs) are associated with liver fibrosis development. To date, there are no FDA-approved drugs for the treatment of liver cirrhosis. Augmentation of HSCs apoptosis is one of the resolutions for liver fibrosis. In this study, we extracted α-mangostin (1,3,6-trihydroxy-7-methoxy-2,8-bis(3-methyl-2-butenyl)-9H-xanthen-9-one) from the fruit waste components of mangosteen pericarp. The isolated α-mangostin structure was determined and characterized with nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) and compared with those known compounds. The intracellular signaling pathway activities of α-mangostin on Transforming growth factors-beta 1 (TGF-β1) or Platelet-derived growth factor subunit B (PDGF-BB) induced HSCs activation and were analyzed via Western blot and Real-time Quantitative Polymerase Chain Reaction (Q-PCR). α-Mangostin-induced mitochondrial dysfunction and apoptosis in HSCs were measured by seahorse assay and caspase-dependent cleavage. The in vivo anti-fibrotic effect of α-mangostin was assessed by carbon tetrachloride (CCl₄) treatment mouse model. The data showed that α-mangostin treatment inhibited TGF-β1-induced Smad2/3 phosphorylation and alpha-smooth muscle actin (α-SMA) expression in HSCs in a dose-dependent manner. Regarding the PDGF-BB-induced HSCs proliferation signaling pathways, α-mangostin pretreatment suppressed the phosphorylation of extracellular-signal-regulated kinase (ERK) and p38. The activation of caspase-dependent apoptosis and dysfunction of mitochondrial respiration (such as oxygen consumption rate, ATP production, and maximal respiratory capacity) were observed in α-mangostin-treated HSCs. The CCl₄-induced liver fibrosis mouse model showed that the administration of α-mangostin significantly decreased the expression of the fibrosis markers (α-SMA, collagen-a2 (col1a2), desmin and matrix metalloproteinase-2 (MMP-2)) as well as attenuated hepatic collagen deposition and liver damage. In conclusion, this study demonstrates that α-mangostin attenuates the progression of liver fibrosis through inhibiting the proliferation of HSCs and triggering apoptosis signals. Thus, α-mangostin may be used as a potential novel therapeutic agent against liver fibrosis. Full article

Pseudo-multicomponent reactions (Pseudo-MCRs) have led to a variety of compounds with interesting biological properties, especially desirable in the pharmaceutical industry. The isatin nucleus could be considered a privileged scaffold for the design of biologically active substances. Dimedone is an interesting and versatile molecule for most organic transformations, especially one-pot and multicomponent reactions. Xanthene derivatives are still an attractive research field for both academia investigations and industry. In this investigation, a simple and efficient tandem Knoevenagel–Michael protocol with subsequent cyclization for the synthesis of the previously unknown 4a′-hydroxy-3′,3′,5,6′,6′,7-hexamethyl-3′,4′,4a′,6′,7′,9a′-hexahydrospiro[indole-3,9′-xanthene]-1′,2,8′(1H,2′H,5′H)-trione was elaborated. The suggested method is based on the pseudo-MCR of 5,7-dimethylisatin and dimedone. The structure of the earlier unknown compound was proven using ¹H, ¹³C-NMR, and IR spectroscopy, mass spectrometry, and elemental analysis. To compare the developed protocol with the existing ones, unsubstituted spiro[indole-3,9′-xanthene] was synthesized. Its structure has been proven using two-dimensional (2D) NMR spectroscopy techniques. Full article

Contrary to the 4′- and 5′-nitro- and aminofluoresceins, the corresponding 3′-derivatives are practically unexplored. In this paper, we describe the synthesis and spectral properties of 3′-nitrofluorescein and 3′-aminofluorescein, as well as their methyl esters. Among other methods, X-ray analysis, ¹³C NMR spectroscopy, and ESI mass spectrometry made it possible to establish the molecular structure of the target compounds as well as intermediates and by-products. Some unexpected products, though in small amounts, were revealed within the course of study. Whereas the fluorescence of the double-charged R²⁻ ion of 3′-nitrofluorescein in both aqueous and organic solvents is weak, the R²⁻ anion of 3′-aminofluorescein in a non-hydrogen bonding donor solvent, but not in water, exhibits intensive fluorescence, analogous to the case of 4′- and 5′-aminofluoresceins. Interestingly, the ${\lambda }_{\max }$ values in water of the R²⁻ ions bearing an NO₂ group in the 3′- and 6′-positions are 7 to 10 nm higher than those of the 4′- and 5′-nitro derivatives. The difference was also observed in dimethyl sulfoxide. This correlates with the angles between the xanthene and phthalic planes of the dyes. The dye 3′-aminofluorescein could be used as a fluorescent indicator sensitive to hydrogen bonding ability of the solvent. It could also serve as a platform for synthesizing fluorescent molecular probes for biochemical research, analogous to the very popular application of 4′- and 5′-amino derivatives. Full article

Lead (Pb²⁺) ions are considered as one of the primary environmental pollutants and have a profound effect on human health. In this work, we have developed a hybrid organic–inorganic optical nanochemosensor for selective and ultrasensitive detection of Pb²⁺ ions based on energy transfer (ET), involving a Pb²⁺ sensitive rhodamine-derived named (E)-4-(((3′,6′-bis(diethylamino)-3-oxospiro[isoindoline-1,9′-xanthen]-2-yl)imino)methyl)benzaldehyde represented as RBDA, covalently linked with silica coated upconverting nanophosphors (UCNPs). The UCNPs emit visible light after being excited by NIR light, activating the Pb²⁺ coordinated RBDA (fluorescent probe). When Pb²⁺ ions were added, a yellow emission band at about 588 nm formed in upconverting photoluminescence spectra, whereas the strength of green emission at about 542 nm reduced upon excitation of 980 nm laser, indicating the energy transfer from UCNP to RBDA-Pb²⁺ complex. The concentration of Pb²⁺ ions directly affects how well the probe reabsorbs the green emission of the nanophosphor, thus enabling the ratiometric chemosensing. With a detection limit of 20 nM in aqueous, the resulting ET-based nochemosensor can also preferentially detect Pb²⁺ despite the presence of other ions. Owing to the minimal autofluorescence and the great penetration depth of NIR light and special optical features of UCNPs, this is a promising approach for sensitive and in-depth detection of Pb²⁺ ions in a complex ecological and biological specimen. Full article

An efficient and environmentally benign one-pot condensation of cyclic diketones, aldehydes and naphthols was achieved with 1,4-diazabicyclo[2-2-2]octane supported on Amberlyst-15 as a novel catalyst, producing a variety of benzoxanthenones in good to excellent yields. The advantages of this multicomponent reaction include the use of a heterogeneous catalyst, solventless conditions and a simple methodology that is atom-economical and results in low E-factor values. A total of 17 xanthene derivatives, including two novel molecules, were synthesized and then characterized. Aromatic aldehydes carrying an electron-withdrawing group provided excellent yields. Appreciable results were also obtained using aliphatic aldehydes. The catalyst is fully recyclable and can be reused up to six times. Full article

The most widely used material as a hole-transport layer (HTL) for effective normal perovskite solar cells (PSCs) is still 2,2′,7,7′-Tetrakis[N, N-di(4-methoxyphenyl)amino]-9,9′-spirobifluorene (Spiro-OMeTAD), which requires heavy doping with the hydroscopic Lithium bis(trifluoromethanesulfonyl)imide (Li-ΤFSI). However, the long-term stability and performance of PCSs are frequently hampered by the residual insoluble dopants in the HTL, Li⁺ diffusion throughout the device, dopant by-products, and the hygroscopic nature of Li-TFSI. Due to the high cost of Spiro-OMeTAD, alternative efficient low-cost HTLs, such as octakis(4-methoxyphenyl)spiro[fluorene-9,9′-xanthene]-2,2′,7,7′-tetraamine) (X60), have attracted attention. However, they require doping with Li-TFSI, and the devices develop the same Li-TFSI-derived problems. Here, we propose Li-free 1-Ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide (EMIM-TFSI) as an efficient p-type dopant of X60, resulting in a high-quality HTL with enhanced conductivity and deeper energy levels The optimized X60:EMIM-TFSI-enabled devices exhibit a higher efficiency of 21.85% and improved stability, compared to the Li-TFSI-doped X60 devices. The stability of the optimized EMIM-TFSI-doped PSCs is greatly improved, and after 1200 hr of storage under ambient conditions, the resulting PSCs maintain 85% of the initial PCE. These findings offer a fresh method for doping the cost effective X60 as the HTL with a Li-free alternative dopant for efficient, cheaper, and reliable planar PSCs. Full article

Horseradish peroxidase (HRP) combined with its fluorescence substrates is attracting increasing attention for biochemical analysis. Amplex red is the most widely used fluorescence substrate to HRP; however, it suffers from some drawbacks, such as nonspecific responsiveness toward carboxylesterases. Discovering a new small molecular fluorescence substrate with improved sensitivity and selectivity for HRP is thus desired. Herein, three dihydrofluorescein derivatives (DCFHs) are presented to serve as HRP substrates through fluorescence turn-on methods. The most promising one, 2,7-dichloro-9-(2-(hydroxymethyl)phenyl)-9H-xanthene-3,6-diol (DCFH-1), exhibited excellent sensitivity in the detection of HRP. Moreover, DCFH-1 does not respond to carboxylesterase, thus holding advantages over Amplex red. In the further study, the detection reagent in the commercial ELISA kits was replaced with DCFH-1 to establish a new fluorescence ELISA, which works very well in the quantification of inflammatory cytokine biomarkers from in vitro models. Full article

The rise of multidrug resistance (MDR) bacteria in nosocomial and health-care institutions is widespread and is currently recognized as a major medical challenge. Mechanisms of bacterial resistance, namely, quorum sensing (QS), biofilm formation, and efflux pumps, have been identified as critical biological processes in MDR bacteria. Following previous reports on the activity of phenothiazines against mechanisms of bacterial resistance, in this work we focus on the synthesis of xanthene derivatives aiming to discover phenothiazine bioisosteres with improved activity. Four compounds were obtained from the conjugation of xanthydrol with sulfonamides and aniline and were fully characterized. Their antibacterial activity was assessed considering their minimum inhibitory concentration (MIC) against Gram-positive and Gram-negative strains, efflux pump inhibition, influence on biofilm formation and quorum-sensing (QS) inhibition. It was observed that the MIC of all the tested compounds was above 64 µg/mL The four 9-xanthenyl derivatives obtained, particularly the xanthene sulfonamide derivatives 3b and 3c, showed promising results on QS inhibition with a reduction of pigment production of 48 and 41 mm, and on biofilm formation with a reduction of 78 and 79%, respectively. Full article