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Tocopherol-Doxorubicin Conjugate as a Lipid-Prodrug: Synthesis methods, Self-assembly, Breast Cancer Cell Inhibition, and Theoretical Analysis

Developing natural lipid-based conjugates/prodrugs emerged as a promising topic in pharmaceutical chemistry and biomedicine. Based on our prior works on natural lipid-based gene/drug delivery systems, in this work, a natural antioxidant lipid, α-Tocopherol (vitamin E), was covalently connected with Doxorubicin (Dox, a topoisomerase II inhibitor) to synthesize a Toco-Dox conjugate through two approaches: Triphosgene activation (method A) and 4-nitrophenyl chloroformate (method B) activation methods. Regarding the green chemistry issues, Triphosgene (method A) easily decomposes into extremely lethal phosgene gas (used as a chemical weapon in WWI ), in contrast, 4-Nitrophenyl chloroformate is non-volatile and generates safe-to-handle byproduct 4-nitrophenol (does not release any toxic gas), making it much less hazardous and more eco-friendly. Molecular structure and purity of the Toco-Dox was characterized by 1H and 13C NMR, FT-IR, MALDI-TOF-MS and UHPLC. Toco-Dox could self-assemble into prodrug nanoparticles (NPs) in the DMSO/water mixture, and the related physico-chemical properties of Toco-Dox NPs were characterized by DLS. Moreover, The physicochemical and biological properties of Toco-Dox (Dox as a control) were theoretically calculated or viruallly analyzed. In addition, MCF-7 breast cancer cell inhibition (cytotoxicity) and intracellular localization of the Toco-Dox was preliminarily evaluated. This work provided efficient approaches for developing natural hydrophobic vitamine (lipid)-based prodrug delivery systems.

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"Bioactive potential of the Ethyl Acetate Extract from Prosopis laevigata: Antimicrobial and Anti-inflammatory effects"

Introduction
Antimicrobial resistance (AMR) occurs when treatment of infections caused by viruses, bacteria, fungi, or parasites becomes ineffective, allowing the microorganism to persist in the host, leading to the spread of disease, its progression, or even death. This phenomenon represents a threat to the global health progress. Considering the increasing demand for alternative therapies with fewer side effects, this study aimed to evaluate the antimicrobial and anti-inflammatory activity of the ethyl acetate extract of
Prosopis laevigata.

Results and Discussion
The chromatographic analysis of the ethyl acetate extract from
Prosopis laevigata was carried out by High-Performance Liquid Chromatography (HPLC) at a detection wavelength of 330nm. A significant retention time was observed at 13.917 min (λmax = 199.0, 253.3 and 349.4nm), suggesting this compound corresponds to luteolin. Fraction R9 showed antimicrobial activity against 11 strains, including Staphylococcus aureus, S. epidermidis, K. pneumoniae, P. aeruginosa, S. dublin and Candida albicans. In the TPA-induced inflammation model, R9 reduced edema to 2.675 mg, R4 to 2.850 mg, and R7 to 3.450 mg. The positive control (indomethacin) showed significant inhibition with 1.380 mg. These values correspond to inhibition rates of 75.74%, 74.15%, and 68.71%. Statistical analysis showed anti-inflammatory effects comparable to indomethacin. The results were analyzed using one-way ANOVA and Dunnett’s post hoc test (p ≤ 0.05).

Experimental Section
The antimicrobial activity was determined by minimal inhibitory concentration (MIC) against 14 strains. Anti-inflammatory activity was tested using a TPA-induced ear edema model in ICR mice. HPLC-PDA was used to analyze the extract’s chemical profile.

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Halogenated Cinnamanilides and Their Activity against Selected Gram-negative Bacteria

Recently published halogenated anilides of chlorinated and trifluorinated cinnamic acids, such as (2E)-N-[3,5-bis(trifluoromethyl)phenyl]-3-(3,4-dichlorophenyl)prop-2-enamide, (2E)-N-(3,5-dichlorophenyl)-3-[3-(trifluoromethyl)phenyl]prop-2-enamide or (2E)-N-[3,5-bis(trifluoromethyl)phenyl]-3-[4-(trifluoromethyl)phenyl]prop-2-enamide, showed excellent antibacterial activities in vitro against Gram-positive bacteria, especially against reference and quality control strains Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, as well as against representatives of multidrug-resistant bacteria and clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE) with minimum inhibitory concentrations (MICs) against staphylococci <0.2 µg/mL and against enterococci <4 µg/mL. It should be noted that all these compounds are rather lipophilic (software predicted log P values close to 5) and carry electron-withdrawing substituents that allow them to be classified as so-called Michael acceptors. All these facts inspired further investigation of the spectrum of effectiveness against other bacteria, and the most effective agents with various substitutions in both the anilide part and on the phenyl ring of the parent cinnamic acid were chosen and tested against selected pathogenic Gram-negative bacteria, such as reference and quality control strains Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27859 and clinical isolate of Klebsiella pneumoniae 797. Unfortunately, it was found that none of the selected halogenated anilide derivatives with such high potency against Gram-positive bacteria demonstrated better efficacy against the tested Gram-negative bacteria than MICs 256 µg/mL.

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Sustainable conjugated polymer synthesis in OPV: a case study from conventional to flow and microwave-assisted synthesis

Organic photovoltaics (OPVs) emerge as a promising alternative to silicon-based solar cells, especially for indoor applications, due to their lightweight, flexibility, and potential for low-cost production. A key challenge remains the development of scalable and environmentally friendly methods for synthesizing conjugated polymers, essential components of the active layers in OPV devices. To increase their economic viability and their sustainability, it is essential to combine low-cost, large-scale module production with greener conjugated polymer production and minimal batch-to-batch variation.

Continuous flow and microwave-assisted syntheses represent two efficient, sustainable approaches aligned with green chemistry principles. Continuous flow significantly reduces reaction times and solvent use, while microwave-assisted methods further enhance sustainability by minimizing solvent consumption and energy input, and enabling faster reactions. These advanced methods can thus play a crucial role in developing next-generation OPV materials in a more cost-effective and environmentally responsible way.

Here we present the case study of PSBTBT (poly(4,4-dioctyldithieno(3,2-b:2',3'-d)silole)-2,6-diyl-alt-(2,1,3-benzothiadiazole)-4,7-diyl), a low band gap electron-donating polymer for OPVs. We have developed the PSBTBT Stille cross-coupling polymerization using different approaches: conventional, continuous flow and microwave-assisted methods. To assess the impact of the different synthetic methods, we performed molecular and spectroscopic characterization to highlight correlations between the synthesis technique and the resulting material properties.

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UV-Visible spectrophotometric determination of Vonoprazan Fumarate in Pharmaceutical Formulation through Complex Formation with Cu(II) and Fe(II) ions
, , , , , , ,

A simple, sensitive and reproducible spectrophotometric method is developed for the determination of Vonoprazan(VPZ) in pharmaceutical formulation. The developed method involved the formation of colored binary Complexes I and Complex II between the VPZ and Copper (II) and Iron (II) ions, respectively. The maximum absorbance values for Complex I and Complex II were at wavelengths of 265 nm and 360 nm, respectively. The stoichiometry of the reaction between the VPZ and Copper (II) is found to be 5:5, while for Vonoprazan and Iron (II) was found to be 7:3. The Calibration curve obtained by Beer’s law, has a linear domain in the concentration ranges of 0.001M to 0.01M for both metals. The limit of Detection (LOD, calculated as: LOD = 3 ´ sa/slope) and the limit of quantification (LOQ, calculated as LOQ = 10 ´ sa/slope). The estimated values are LOD = 4.24 ´ 10-7 M and LOQ = 1.41 ´ 10-6 M for Complex I and LOD = 3.04 ´ 10-7 M and LOQ = 1.01 ´ 10-6 M for Complex II, respectively. The validity of the proposed method was assessed. Statistical analysis of the results has been carried out, revealing high accuracy and good precision. The proposed methods for the determination of VPZ in pharmaceutical formulation are rapid, simple, sensitive, and can be comparable with other sophisticated techniques for quality control applications.

  • Open access
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STYRENE-DIVINYLBENZENE COPOLYMERS FUNCTIONALIZED WITH AMINOACID GROUPS: SYNTHESIS, PHYSICOCHEMICAL CHARACTERIZATION

Styrene-divinylbenzene resins are synthetic copolymers known for their chemical resistance, mechanical durability, and good porosity . Amino acids contain functional groups such as amines (-NH₂), carboxylic acids (-COOH). Many of them are natural and non-toxic, making them ideal for applications in biomedical devices, drug delivery, and tissue engineering. This work investigates the physicochemical characterization of two copolymer supports, (containing 6.7% and 15% DVB), functionalized with aminoacid. The syntheses to obtain AP1 and AP2 were performed as presented in a previous paper. FTIR analysis shows shifts in C=O, C–N, and C–H bands at 1510–1365 cm⁻¹ and broad OH/NH absorption at 3510 cm⁻¹, confirming the copolymer's functionalization. EDX analysis of AP1 and AP2 confirmed the presence of nitrogen, with concentrations ranging from 0.4% to 0.5%. TGA was further employed to investigate the impact of grafted aminoacid groups on the thermal stability and decomposition behavior of the copolymers. Thermal stability, as indicated by residual mass at 900 °C, follows the trend:S-6.7%DVBCH₂Cl > AP2 (21.72%) > S-15%DVBCH₂Cl > AP1 (15.52%). AP1 exhibits a greater mass loss (84.48%) compared to S-15%DVB (80.82%), indicating a more significant degradation of its polymer structure. AP2 shows a slightly lower weight loss (78.28%), suggesting improved thermal stability, likely due to structural modifications involving aminoacid functional groups. The differences in functionalization and degree of crosslinking between AP1 and AP2 contribute to AP2’s more thermal stability.

  • Open access
  • 8 Reads
Integration of CO/PES support modules for enhancement of modified-chitosan filtration membranes

The impact of plain cotton (CO) and polyester (PES) fabric support modules on the filtration performance of chitosan/silver nanoparticles/graphene oxide (CS/AgNP/GO) was determined in this study. The experimental results revealed that both the CO and PES fabrics can successfully serve as support modules for CS/AgNP/GO composite membranes, increase water permeability, and effectively improve the filtration process. The CO fabric-supported membranes displayed more irregular and non-uniform cross-sectional intensities, while the polymer membranes with PES support showed a relatively smoother and more evenly distributed cross-sectional structure. However, the effectiveness of the membrane separation process depends on effective molecular interaction between the composite structure and the support materials. Although both fabric- supported modules improved membrane wettability adequately, the CO is more hydrophilic than the PES of approximately the same thickness. This was attributed to higher wettability and capillary pore sizes within the molecular structure of the CO-supported membrane, which gave higher water absorbency of 24.7% than the PES-supported modified CS composite over the same duration of time, confirming greater adhesive force with improved hydrophilicity. The improved chemical bonding between the CS composite and the support modules resulted in an increase in mechanical properties. The maximum tensile strength of 48.46 MPa was attained by the CO-supported composite, followed by the PES-supported modified CS filtration membrane (43.73 MPa), while the non-fabric-supported membrane exhibited the lowest tensile strength of 43.73 MPa with the highest elongation at break (64.2%).

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Docking and in silico ADMET analysis of flavone glucoside compounds as antioxidant agents

Natural products continue to serve as a rich source of structurally diverse compounds with significant therapeutic potential. Among them, flavonoids an important class of polyphenolic secondary metabolites are widely distributed in plants and have attracted considerable interest due to their broad spectrum of biological activities. These include antioxidant, anti-inflammatory, and anticancer effects, as well as the inhibition of key metabolic enzymes such as xanthine oxidase (XO). XO is a critical enzyme in purine catabolism, catalyzing the oxidation of hypoxanthine to xanthine and subsequently to uric acid, a process that also generates reactive oxygen species (ROS) as by-products. Overactivity of XO, and the resulting accumulation of uric acid and ROS, has been associated with various pathological conditions, including gout and oxidative stress-related disorders. Consequently, XO inhibition represents a promising strategy for therapeutic intervention.
In this study, we investigated the xanthine oxidase inhibitory potential of two flavone glucoside compounds : chavicol-1-O-(6′-O-methylmalonyl)-β-D-glucopyranoside and chavicol-1-O-(6′-O-acetyl)-β-D-glucopyranoside which were previously isolated from the aerial parts of Agastache rugosa. Molecular docking analysis was performed to evaluate their binding affinity toward the XO active site. Both compounds exhibited strong interactions with key active site residues, achieving docking scores of approximately -7 kcal/mol, which are comparable to that of the well-known XO inhibitor, quercetin. The docked ligands formed critical hydrogen bonds with residues such as Lys771 and Ser876, along with hydrophobic contacts within the enzyme's active pocket.
In addition, ADMET profiling was conducted to assess the pharmacokinetic and physicochemical properties of the compounds

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MOLECULAR MODELLING OF WITHANOLIDES AGAINST EP2 RECEPTOR FOR TREATMENT OF ENDOMETRIAL CANCER: A PHARMACOKINETIC AND MOLECULAR DOCKING STUDY

Endometrial cancer is one of the most common gynecological cancers, with global new cases, approximately 420,000 new cases and 98,000 global deaths annually. Emerging evidence suggests that the prostaglandin E2 receptor (EP2) plays a critical role in tumor progression, angiogenesis, and immune evasion. Withanolides, a class of naturally occurring compounds, possess anticancer activity; however, effect on EP2 receptor in endometrial cancer remains largely unexplored. This study aims to explore the interaction between Withanolides and EP2 receptor using molecular docking techniques, with PF-04418948 as the reference antagonist. A select number of these ligands, with anti-cancer activity, were evaluated for their ADMET and toxicity properties, and those with favorable drug-like properties, low toxicity profile, and no more than 1 Lipinski’s rule violation, were docked to EP2 (PDB ID: 7CX2). Molecular docking studies revealed three ligands, (Pubchem 161671, 265237, and 21679027) with significantly higher binding affinity scores compared to that of the reference compound. Pubchem 161671, showed the highest binding affinity at -16.6 kcal/mol. Post-dock analysis revealed interactions with key amino acids, VAL89, LEU298, SER305, and MET31, which are essential for the antagonist activity of the EP2 receptor enzyme (Yano et al., 2017). Significant interaction with critical amino acid residues suggested potential inhibition of EP2 receptor activity, offering a potential therapeutic approach for treating endometrial cancer. Overall, this study profers a deeper understanding of the potential of Withanolides as leads for EP2 targeted therapy in endometrial cancer.

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Computational Insights into the Open–Closed Equilibrium of Substituted Spiropyrans: Stability and Optical Properties

Spiropyran (SP)–merocyanine (MC) systems are dynamic molecular switches that have been widely studied for their tunable optical properties. The equilibrium between the closed (SP) and open (MC) forms can be modulated by structural features, enabling their application in sensing, photoresponsive materials, and fluorescence-based devices. In a recent experimental study by Alonso et al., two SP–MC pairs were synthesized: one bearing a single hydroxyl substituent on the aromatic ring (SP1/MC1), and another featuring a tri-hydroxylated aromatic moiety, also known as gallol (SP3/MC3). While SP1 predominantly adopts the closed configuration, the second system exists exclusively in the open MC3 form and exhibits strong fluorescence.

Herein, we present a computational study based on density functional theory (DFT) to rationalize these differences. Conformational searches using xTB/CREST were followed by geometry optimizations (B97-3c) and single-point energy calculations (B3LYP-D4/def2-TZVP). Relevant properties, including relative free energies, dipole moments, charge distribution, and orbital energies, were evaluated. TDDFT calculations (CAM-B3LYP/def2-TZVP) were employed to simulate UV–Vis absorption and explore fluorescence behavior. Solvent effects were modeled using the SMD model to assess the influence of polarity on the SP–MC equilibrium as well as on the optical properties.

This computational analysis aims to test the hypothesis that gallol substitution (SP3/MC3) stabilizes the MC configuration. The results are expected to clarify the impact of substitution and solvation on structural and optical properties, providing insights for the rational design of fluorescent photoactive molecules with tunable SP–MC interconversion.

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