Search Results (193)

Chromene derivatives are important structural motifs in biologically active compounds and functional materials, and the development of efficient strategies for their synthesis remains of considerable interest. In this work, simple and sustainable methodologies were developed for the synthesis of chromene dimers linked through short amidine/geminal diamine spacers or long, flexible alkyl diamine linkers. The amidine and geminal diamine linkers were obtained from 3-aminochromene derivatives via nucleophilic addition of the amino group to triethyl orthoformate or non-phenolic aldehydes in ethanol, at room temperature or under reflux, affording the corresponding dimers in moderate to very good yields. In a complementary approach, flexible alkyl diamide linkers were prepared from diamines and ethyl cyanoacetate, followed by condensation with salicylaldehydes in aqueous hydrogen carbonate solution and subsequent acidic hydrolysis, leading to new chromene dimers in excellent yields. These mild and operationally simple protocols provide efficient access to structurally diverse chromene dimers with potential applications in medicinal chemistry and materials science. Full article

The multidirectional bioactivity of betulin (BN), its widespread occurrence in plants, relatively low toxicity, and acceptable safety profile make it an attractive scaffold for scientific research and potential therapeutic applications. Due to the presence of reactive functional groups (C-3-OH and C-28-OH), BN is an interesting source of new semisynthetic bioactive compounds obtained via structural modifications of the parent backbone. In our study, we designed new BN–amino acid (BNAA) molecular hybrids, aiming to exploit synergistically the properties of both components. We prepared and evaluated a total of 18 new compounds for antitumor activity against the two human cancer cell lines (HCT 116 and MCF-7) and one non-cancerous cell line (NHDF) using a standard Cell Counting Kit-8 (CCK-8) assay. The potential signaling pathways of the obtained BN derivatives were identified based on the measurement of p21 and Bax mRNA expression levels using the RT-qPCR method. We successfully synthesized a series of new BN hybrids by conjugation of the C-3 and C-28 hydroxyl groups via a succinyl (-CO-CH₂-CH₂-CO-, Suc) linker with selected amino acid methyl esters. The structures of all obtained BNAA molecular hybrids were confirmed by spectroscopic analysis (¹H and ¹³C NMR) and high-resolution mass spectrometry (HR-MS). Analysis of the biological activity of the obtained BN derivatives indicated that both the attached amino acids and the substituents at C3 carbon alter BN activity. The obtained BN–amino acid hybrids represent a useful platform for further optimization, especially derivatives (3a, 3e, 3f, and 7d), which showed the most relevant biological profiles in this study. Full article

N-Methyl-D-aspartate (NMDA) receptors are ligand- and voltage-gated ion channels essential for synaptic plasticity, learning, and memory. The GluN2B subunit, highly expressed in the forebrain and spinal cord, is implicated in multiple neurological and psychiatric disorders, making it an attractive target for positron emission tomography (PET) imaging. However, the development of selective GluN2B PET radioligands remains challenging. Here, we describe the design, synthesis, and evaluation of eighteen 3-alkylaryl derivatives of 7-methoxy-2,3,4,5-tetrahydro-1H-benzo[d]azepin-1-ol, including enantiomerically resolved compounds, as candidate PET radioligands. Structure–activity relationship studies show that binding affinity is largely insensitive to electronic and steric variation at the terminal aryl group but strongly dependent on alkyl linker length, with a four-carbon chain providing optimal affinity. Binding affinity does not correlate with calculated lipophilicity, suggesting hydrophobicity is not the primary determinant of receptor interaction. Absolute configuration was established using vibrational circular dichroism and infrared spectroscopy, and docking studies provided insight into enantiomer-specific binding modes. Two ligands, L3 and L6, and their enantiomers exhibited high GluN2B affinity, favorable physicochemical properties, and suitability for carbon-11 labeling. Separate PET imaging studies confirmed strong and specific brain binding of the radiolabeled compounds. These findings establish this scaffold as a promising platform for GluN2B PET ligand development. Full article

Selective inhibition of the tumour-associated carbonic anhydrase (CA) isoforms IX and XII, which are overexpressed in hypoxic tumours, has emerged as a promising strategy for the development of novel anticancer agents. Among the diverse CA inhibitors reported to date, coumarins have attracted particular attention. These chromenone derivatives, widely distributed in phytochemicals, display a broad range of biological activities and are known to act as suicide inhibitors of CAs. Following the tail approach, we designed a series of hybrid compounds combining a coumarin core with an N-arylthioureido scaffold located at the C-7 position and investigated how structural variations—including substituents on the coumarin and aromatic moieties, tether length, and urea/thiourea isosterism—influence their biological properties (CA inhibition and antiproliferative activity). Substituted coumarins at C-3 and C-4 were efficiently prepared via Pechmann condensation, while the thioureido motif was introduced using various aryl isothiocyanates as key synthetic intermediates. The lead compound, featuring a dimethylated coumarin, a pentyl linker, and an N-(p-tolyl)thioureido residue, inhibited the target enzymes in the low- to mid-nanomolar range (K_i = 6.0 and 49.9 nM, respectively), displaying selectivity indexes (S.I.s) surpassing those of the reference drug acetazolamide (AAZ). Moreover, it exhibited potent antiproliferative activity, with GI₅₀ values in the low micromolar range (1.9–3.5 µM) against both drug-sensitive and multidrug-resistant cancer cell lines. Label-free three-dimensional holotomographic microscopy revealed that this compound triggers slow apoptosis, leading to cell death after approximately 20 h of exposure. Full article

The widespread use of herbicides such as paraquat and glyphosate is a serious environmental and health concern due to their persistence, mobility, and toxicity in aquatic ecosystems. Composites of alginic acid (Alg) are prepared with carbonaceous materials such as graphene oxide (GO), carbon particles (CPs), porous carbon particles (PCPs), carbon black (CB), and carbon nanotubes (CNTs) were synthesized and evaluated as sorbents for the removal of cationic herbicide paraquat and the anionic herbicide glyphosate. The resulting Alg-based beads are environmentally safe because of the materials used during their preparation, such as a biopolymer, Alg, carbonaceous substances (GO, CPs, PCPs, and CB) as composite moieties, and Ca(II) ions as cross-linkers. The Alg–bead composite possessed strong swelling ability ranging from 1700% to 2500%, which led to swollen beads of spherical shape and an average diameter of 3 mm, each containing 20% of carbonaceous materials. Amongst all Alg-based beads prepared for paraquat and glyphosate removal from the aquatic environment, the highest adsorption capacity was attained for Alg–porous carbon particle (Alg-PCP) composites. The Alg-PCP beads were capable of adsorbing 85.7 ± 2.9 mg/g and 31.6 ± 2.2 mg/g from 50 mL of 250 ppm solutions of paraquat and glyphosate, respectively. In contrast, bare Alg beads adsorbed only 39.7 ± 1.8 mg/g and 12.9 ± 1.7 mg/g, respectively. A 250 mg Alg-PCP bead composite achieved a 91% removal of paraquat from a 50 mL solution containing 250 ppm of paraquat. These results show that Alg–PCP can be used to mitigate herbicide contamination in water, protecting aquatic ecosystems and addressing associated environmental and health risks. Full article

Ochratoxin A (OTA) is a highly toxic mycotoxin commonly detected in food and agricultural products, requiring sensitive analytical methods for reliable monitoring. Herein, we report an ultrasensitive turn-on electrochemical aptasensor for OTA detection based on a target-induced displacement of an aptamer–complementary DNA (cDNA) duplex assembled on an electrochemically reduced graphene oxide (ERGO)-modified glassy carbon electrode (GCE). In the absence of OTA, a methylene blue (MB)-labeled aptamer hybridized with cDNA is immobilized on the ERGO surface via π–π stacking interactions, forming a rigid duplex that suppresses electron transfer and yields a low electrochemical signal. Upon OTA binding, the aptamer undergoes a conformational transition into a G-quadruplex structure, leading to dissociation of the cDNA strand. This target-induced folding brings the MB redox tag into close proximity to the ERGO surface, markedly accelerating electron transfer and enhancing the cathodic reduction current of MB, thereby producing a pronounced signal-on response in square-wave voltammetry (SWV). The ERGO-modified electrode provides a conductive and stable interface without chemical linkers. Under optimized conditions, the aptasensor shows a linear response to OTA from 10 fM to 100 pM with an ultralow LOD of 0.67 fM, together with high selectivity, good reproducibility, and satisfactory stability. This work demonstrates a simple and effective turn-on aptasensing strategy for sensitive electrochemical detection of OTA. Full article

We synthesized seven carbocyclic nucleoside analogs featuring a cyclopentane ring in place of the (deoxy)ribose sugar, which serves as a linker in DNA/RNA nucleosides. We assessed the stability of cyclopentane nucleosides in 98% w/w sulfuric acid at room temperature via ¹H and ¹³C NMR spectroscopy. We observe that adenine (A1, A4), guanine (G1) and thymine (T1) cyclopentane nucleoside analogs remain stable for at least two weeks at room temperature, with only minor (~4%) degradation in A1. In contrast, the cytosine analog (C1) rapidly degrades to release a soluble cytosine. Methyl-substituted adenine analogs mimicking polymer backbone attachments at positions prone to tertiary carbocation formation (A2, A3) prove unstable and release soluble adenine. Only the 3,3-dimethylcyclopentyl adenine analog (A4) exhibits sufficient stability. Our findings reveal that cyclopentane serves as a viable stable linker in concentrated sulfuric acid for select nucleic acid bases, provided that the backbone connections avoid tertiary carbons susceptible to carbocation-mediated cleavage. We thus identify one potential key structural feature for engineering examples of genetic-like polymers that could potentially persist in Venus’s concentrated sulfuric acid cloud environment. Full article

Tuberculosis, caused by Mycobacterium tuberculosis, remains a global health challenge, particularly due to multidrug-resistant strains. Photodynamic therapy using porphyrin-based photosensitizers offers a promising alternative by targeting the trehalose-rich cell wall of the bacillus. Motivated by prior experimental observations that shorter linkers improve efficacy, this study probes the molecular basis of linker-length-dependent activity in trehalose–porphyrin glycoconjugates. Here, we show that shorter linker lengths are consistent with improved activity in vitro and, in an Ag85B docking model, constrain conformational flexibility, reduce solvent exposure, and promote tighter packing consistent with stronger predicted interactions. Using computational docking, we analyzed binding scores, RMSD variability, steric clashes, and protein–ligand interactions for conjugates docked into Ag85B, a key enzyme in cell wall synthesis. Shorter linkers (0–2 carbons) were found to exhibit superior binding scores, lower RMSD variability, and stronger interactions with residues such as ARG 43, including unique π–cation interactions. In contrast, longer linkers displayed increased flexibility, reduced binding specificity, and greater solvent exposure. These findings, which support our experimental observations, suggest a molecular basis for linker-dependent efficacy and provide a framework for designing next-generation porphyrin-based therapeutics for tuberculosis treatment. Full article

A novel Lithium triflate-incorporated Solid Polymer Electrolyte (SPE) has been developed by using the optimized blend of Ghatti Gum (GG) and Xanthan Gum (XG) with a biodegradable synthetic polymer, Polyvinyl alcohol (PVA), ethylene glycol as a plasticizer, and formaldehyde as a cross-linker for energy storage applications. They are examined by X-ray diffraction, Fourier transform infrared spectroscopy, and electrochemical impedance analysis. The frequency-dependent conductivity adheres to Joshner’s universal power law, with the TF10 composition achieving the higher ionic conductivity of 2.73 × 10⁻⁵ S cm⁻¹. Temperature-dependent conductivity confirms Arrhenius-type behavior and shows a low activation energy of 0.15 eV that supports facile ion transport. The conduction process in TF10 follows the Correlated Barrier Hopping (CBH) model. Dielectric and modulus investigations indicate relaxation dynamics with the shorter relaxation time (6.45 × 10⁻⁶ s) from tangent loss spectra. From the SEM analysis, the uniform distribution and the porous nature of the electrode activated carbon are confirmed. A supercapacitor is assembled with TF10 displays electric double-layer capacitive features, delivering a specific capacitance of 7.1 Fg⁻¹ at 15 mVs⁻¹. Charge–discharge analysis reveals energy and power densities of 2.52 Wh kg⁻¹ and 2500 W kg⁻¹, respectively, for the supercapacitor. Full article

Background: Carbonic anhydrases (CAs) are known to play important roles in several physiological and pathological processes; among them, CAs IX and XII are of particular relevance in cancer therapy due to their involvement in tumor growth and progression. Methods: In this study, a novel series of benzenesulfonamides incorporating a hydrazinocarbonyl-ureido linker alongside a 6-arylpyridine tail was synthesized and evaluated for inhibitory activity through a stopped-flow CO₂ hydrase assay on four hCA isoforms. Results: Some of the new compounds exhibited great activity and selectivity toward the tumor-expressed CA XII isoform over the off-target isoforms CA I and CA II. Based on these results, they were selected for ADME prediction studies, showing favorable drug-like properties. To further investigate their binding mode, these compounds were docked into the four hCA isoforms. Conclusions: Overall, the results underscore the potential of compounds bearing a 6-arylpyridine tail along with a hydrazinocarbonyl-ureido linker as a foundation for further inhibitor development. Full article

Solar-driven hydrogen production via photocatalytic water splitting represents a promising route toward sustainable and low-carbon energy systems. Among emerging photocatalysts, porphyrin-based framework materials, specifically porphyrinic metal–organic frameworks (PMOFs) and porphyrinic covalent organic frameworks (PCOFs), have attracted increasing attention owing to their strong visible-light absorption, tunable electronic structures, permanent porosity, and well-defined catalytic architectures. In these systems, porphyrins function as versatile photosensitizers whose photophysical properties can be precisely tailored through metalation, peripheral functionalization, and integration into ordered frameworks. This review provides a comprehensive, design-oriented overview of recent advances in PMOFs, PCOFs, and hybrid porphyrinic architectures for photocatalytic H₂ evolution. We discuss key structure–activity relationships governing light harvesting, charge separation, and hydrogen evolution kinetics, with particular emphasis on the roles of porphyrin metal centers, secondary building units, linker functionalization, framework morphology, and cocatalyst integration. Furthermore, we highlight how heterojunction engineering through coupling porphyrinic frameworks with inorganic semiconductors, metal sulfides, or single-atom catalytic sites can overcome intrinsic limitations related to charge recombination and limited spectral response. Current challenges, including long-term stability, reliance on noble metals, and scalability, are critically assessed. Finally, future perspectives are outlined, emphasizing rational molecular design, earth-abundant catalytic motifs, advanced hybrid architectures, and data-driven approaches as key directions for translating porphyrinic frameworks into practical photocatalytic hydrogen-generation technologies. Full article

New arylbenzofuran derivatives were designed, synthesized, and evaluated as potential inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Five hybrid compounds (31–35) feature a 2-phenylbenzofuran core linked via a heptyloxy spacer to an N-methylbenzylamine moiety, to enhance interactions within the active site of BChE. Biological evaluation revealed that brominated derivatives 34 and 35 showed the highest cholinesterases (ChE) inhibition compared to their chlorinated analogs, with compound 34 showing the highest activity for both AChE (IC₅₀ = 27.7 μM) and BChE (IC₅₀ = 0.7 μM). These compounds proved to be non-cytotoxic and demonstrated significant antioxidant activity in SH-SY5Y cells exposed to hydrogen peroxide (H₂O₂), highlighting their potential to mitigate oxidative stress: a key pathological factor in Alzheimer’s disease. Structural activity analysis suggests that bromine substitution at position 7 and the presence of a seven-carbon linker are critical for dual ChE inhibition and selectivity towards BChE. ADMET prediction indicates favorable pharmacokinetic properties, including drug-likeness and oral bioavailability. Overall, these findings highlight the potential of the 2-arylbenzofuran as a promising scaffold for multitarget-directed ligands in Alzheimer’s disease therapy. Full article

Introduction: Chagas disease, caused by the protozoan Trypanosoma cruzi, remains a major public health concern due to the limited effectiveness of current treatments, especially in the chronic stage. Objective: Here, we wanted to advance a library of 30 N,N′-disubstituted diamines as promising antichagasic agents and gain insight into the mechanism of action. Methods: The library was evaluated for activity against the T. cruzi amastigote stage and trypanocidal efficacy. In addition, selected compounds were tested as potential polyamine transport inhibitors, and a fluorescent analog was employed to investigate compound internalization. Results: Five compounds exhibited potent activity (pIC₅₀ > 6.0), particularly those with short aliphatic linkers (3–6 carbon atoms), suggesting a structure–activity relationship favouring shorter chains. Mechanistic studies showed that compound 3c strongly inhibited polyamine transport, a vital pathway in T. cruzi, though this was not a universal mechanism among active hits, indicating the potential for multiple targets. A fluorescent analog confirmed intracellular uptake in amastigotes but lacked antiparasitic activity, likely due to disrupted pharmacophoric features. Importantly, none of the compounds demonstrated trypanocidal activity in long-term assays, and some showed cytotoxicity, particularly in the benzyloxy-substituted series. Conclusions: These findings position N,N′-disubstituted diamines as a viable scaffold for Chagas disease drug discovery. However, further optimization is required to enhance selectivity, achieve trypanocidal effects, and better understand the underlying mechanisms of action. Full article

This study investigates the valorization of two agri-food residues, specifically olive pomace (alperujo, A) and banana peel (B), into efficient N-doped carbon-based catalysts for polluted wastewater treatment. The residues were converted into hydrochar (HA and HB), which were subsequently N-doped using polyethylenimine (PEI) in combination with cross-linkers (glutaraldehyde (GTA) or 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC)) to optimize their catalytic properties. The enhanced hydrochars were utilized as catalysts for the removal of organic pollutants from water by activation of peroxymonosulfate (PMS). Characterization techniques, including CHNS, FTIR, XPS, SEM and electrochemical analysis, were employed to understand the physicochemical properties of the materials. The catalytic activity was evaluated using Reactive Black 5 (RB5) as a model pollutant, with the N-doped alperujo-derived hydrochar cross-linked with EDC (N-HA-EDC) showing the best performance, achieving 80% removal in 60 min and an adsorption capacity of 97 mg/g. The versatility of this functionalization approach was assessed through tests with three pharmaceuticals, corroborating the adaptability and efficacy of the catalyst and demonstrating its potential for wastewater treatment applications. This study provides insights into the development of sustainable, cost-effective carbocatalysts, aligning with circular economy and zero waste principles. Full article

Bufadienolides exert broad-spectrum pharmacological activities relevant to cardiology and novel cancer treatments. Their efficacy, toxicity, and pharmacokinetic profiles are significantly affected by modifications at carbon-3 (C3) of the steroid core. We have applied molecular dynamics simulations to characterize the consequences of (i) variations in size of the substituent at C3, (ii) the type of linker at C3 (ether vs. N-methoxy), and (iii) stereochemistry (C3β vs. C3α) for derivatives’ interactions with Na⁺,K⁺-ATPase. The model compounds included bufalin, bufalin-N-glucose, bufalin-O-glucose as well as digoxigenin, digoxigenin monodigitoxoside and digoxin. It was shown that the optimal size of the substituent is a trade-off between the ability to form stabilizing interactions and steric and entropic interferences. The former is strongly affected by the nature of the linker due to its impact on the spatial position of the ligand: N-methoxy linker imposes rotational restrictions and places the core into a less favorable position compared to an ether bond. Similarly, the change from β- to α-anomer delocalizes the substituent precluding contacts with amino acid residues of the binding site. The presented mechanistic model of bufadienolide interactions with Na⁺,K⁺-ATPase helps to anticipate the consequences of modifications while designing derivatives with high anticancer activity but reduced cardiotoxicity. Full article