Search Results (302)

Background/Objectives: This study aimed to improve the biological profile of oleanolic acid (OA) through structural modification at the C-17 carboxyl group and the C-3 hydroxyl group, with a focus on the design of short-chain alkyl esters and 3-O-furoyl hybrids. Methods: Two series of OA derivatives were synthesized and characterized using spectroscopic methods, including ¹H NMR, ¹³C NMR and MS. In silico structure–activity relationship (SAR) analysis, ADMETox profiling, and molecular docking to the epidermal growth factor receptor (EGFR) tyrosine kinase domain were performed as predictive and hypothesis-generating tools. Anticancer activity was evaluated in vitro using the MTT assay against human cancer cell lines, including HeLa, MCF-7, A-549, SKBR-3, PC-3 and SKOV-3, as well as non-malignant human dermal fibroblasts (HDFs). Antioxidant properties were assessed using cell-free CUPRAC and DPPH assays. Results: The C-17 esterification markedly enhanced cytotoxic potency compared to the parent OA, while the introduction of the 3-O-furoyl moiety further improved antiproliferative activity in several derivatives. Selected compounds showed low-micromolar IC₅₀ values and moderate selectivity toward cancer cells. Molecular docking suggested favorable accommodation of selected derivatives within the EGFR ATP-binding pocket, mainly through hydrophobic and π-related interactions; however, these results do not confirm direct EGFR binding and require experimental validation. The CUPRAC and DPPH assays provided preliminary insight into chemical redox behavior but should not be directly extrapolated to intracellular antioxidant or pro-oxidant activity. Predicted ADMETox profiles indicated moderate permeability and relatively low predicted risk for selected toxicity endpoints, while also highlighting high lipophilicity, poor aqueous solubility and potential metabolic liabilities. Conclusions: Overall, the results identify several OA derivatives as promising anticancer lead compounds for further optimization and mechanistic investigation. Full article

Five pH- and light-switchable punicine derivatives were investigated as collectors in the flotation of spodumene and quartz. At the natural pH of the minerals, the punicine substituted with a C17 alkyl residue showed the best recovery under daylight (>5000 lux), with values up to 65.0% and 97.8%, and also the highest absolute recovery difference between the two minerals. For pH values of 2 and 12, the punicine collector with a viologen moiety and a C9 alkyl residue shows the best absolute recovery difference, with values of 32.45% and 32.88%, respectively. Studies on the influence of pH, particle size distribution, UV light and darkness, ζ-potential measurements, and IR spectroscopic measurements were carried out to gain insight into the mechanisms. Full article

We report the synthesis and characterization of the photophysical characterization of a series of rhodamine (Rho)–perylenebisimide (PBI) electron donor–acceptor dyad/triads containing flexible alkyl spacers (ethylene or hexylene chains). Steady-state absorption and emission, femtosecond and nanosecond transient absorption (fs-TA and ns-TA), cyclic voltammetry, triplet–triplet energy transfer (TTET) experiments and DFT/TD-DFT calculations were combined to elucidate the excited-state dynamics. fs-TA spectral study indicates fast decay of the S₁ state and formation of the ³PBI state (0.32–663 ps), which is supported by the ns-TA spectra. The localized PBI triplet (³PBI*) exhibits unusually long lifetimes (up to 272 μs) as determined by the TTET experiment. No long-lived charge-separated (CS) state was observed. While a Förster resonance energy transfer (FRET) probably occurs between PBI and the open-ring rhodamine, a photo-induced electron transfer is proposed to be responsible for the quenching of the fluorescence of the PBI moiety. Full article

Background/Objectives: The widespread emergence of chloroquine-resistant Plasmodium falciparum continues to drive the search for new quinoline-based antimalarial agents capable of retaining efficacy against resistant parasites. This study aimed to evaluate a series of synthetic quinoline derivatives incorporating arylnitro and aminochalcone moieties for their antiplasmodial activity and selectivity. Methods: A series of eighteen synthetic quinoline derivatives were evaluated for in vitro antiplasmodial activity against P. falciparum strains (3D7, K1, and Dd2), along with cytotoxicity in mammalian cells and hemolytic activity in human red blood cells. Structure–activity relationship analysis was performed, and molecular docking studies were conducted against β-hematin and the chloroquine resistance transporter (PfCRT). Results: Several compounds exhibited sub-micromolar activity against the chloroquine-sensitive 3D7 strain. The most potent compound (Compound 14), a nitro-substituted N-alkylated quinoline bearing a CF₃-enriched aromatic chalcone framework, demonstrated high potency and selectivity (IC₅₀ = 0.13 μM; SI = 1132.92). Importantly, this compound retained substantial activity against multidrug-resistant K1 and Dd2 strains, displaying lower resistance indices than chloroquine. Structure–activity relationship analysis revealed that nitro substitution, N-alkylation, and halogen/CF₃-rich aromatic features critically influence potency and selectivity. Docking studies suggested that Compound 14 engages both β-hematin and PfCRT more extensively than chloroquine. Conclusions: These findings identify Compound 14 as a promising lead scaffold for further optimization toward next-generation antimalarial agents. Full article

A novel series of hybrid tetrahydro-β-carboline (THβC)-imidazolium (IM) salts incorporating a fused diketopiperazine scaffold was designed, synthesized, and evaluated as cholinesterase inhibitors for potential application in Alzheimer’s disease. The molecular design integrates a π-conjugated THβC core with a cationic IM moiety to promote dual-site interactions within the acetylcholinesterase (AChE) active-site gorge. All compounds exhibited micromolar inhibitory activity against AChE and butyrylcholinesterase (BChE), with a pronounced preference for AChE. The most active derivative, 12d, showed an IC₅₀ value of 0.72 μM toward AChE, while compound 12c demonstrated the highest selectivity (SI = 8.4). Structure–activity relationship studies revealed that both stereochemistry and N-alkyl chain length are critical determinants of activity, with S,S-configured derivatives consistently outperforming their R,R-configured analogs. In silico ADMET analysis indicated favorable physicochemical properties and predicted central nervous system permeability, although potential hepatotoxicity highlights the need for further optimization. Molecular docking studies suggested that the most promising compound adopts a dual-binding mode, interacting with both the peripheral anionic site and catalytic active site of AChE. These results identify THβC-IM hybrids as a structurally novel and promising scaffold for the development of selective cholinesterase inhibitors, providing a basis for further optimization toward multifunctional anti-Alzheimer agents. Full article

Background: Ursolic acid (UA) is a natural pentacyclic triterpenoid with notable antitumor activity, yet its poor water solubility and insufficient targeting restrict clinical translation. Methods: Forty novel ursolic acid-phosphine derivatives bearing seven distinct lipophilic cationic moieties were synthesized via C28 modification and structurally characterized by ¹H NMR and ¹³C NMR. Their antitumor activities in PC3-M cells were evaluated via in vitro assays. Mechanistic investigations were performed using transcriptomic analysis and Western blot. Molecular docking was performed to predict the binding profile of Compound 25 with FGFR1. In vivo antitumor efficacy and biosafety were assessed in RM-1 xenograft models in C57BL/6 mice. Results: Compound 25 (bearing a tris(3,5-dimethylphenyl)phosphine group at the C28 position with an alkyl chain length of five methylene units) exhibited the most potent activity against PC3-M cells, dose-dependently inhibiting proliferation, migration, and invasion and inducing apoptosis. It triggered mitochondrial apoptosis via ROS accumulation and disrupted cytoskeletal homeostasis by suppressing the FGFR1/KRAS/RAC1/PIP4K2 axis. Molecular docking results suggested its strong binding affinity and specificity. In vivo studies confirmed its significant antitumor effect and favorable safety. Conclusions: These results highlight the potential of Compound 25 as a promising lead compound and provide valuable insights for further medicinal chemistry optimization and the development of novel anticancer drugs derived from ursolic acid. Full article

Aryl halides are important intermediates for chemical synthesis. However, the negative reduction potential up to −2.7 V (vs. SCE) makes photoredox conversion of aryl halides by reductive dehalogenation to aryl radicals for chemical transformations difficult. Inspired by the outstanding photophysical properties of deazaflavin and triphenylamine, as well as results of theoretical calculations, we attached the diphenylamino group to C8 of deazaflavin, and the resulting compounds look fabricated by “fusing” deazaflavin and triphenylamine (TPA) together by sharing the benzene ring. We also introduced alkyl and aryl moieties to C5 and afforded a series of deazaflavin derivatives (dFLs), namely 10-butyl-8-(diphenylamino)-3,5-dimethylpyrimido[4,5b]quinoline-2,4(3H,10H)-dione (TPAdFlMe), 10-butyl-8-(diphenylamino)-3-methyl-5-(trifluoromethyl)pyrimido[4,5-b]quinoline-2,4(3H,10H)-dione(TPAdFlTF) and 10-butyl-8-(diphenylamino)-3-methyl-5-phenylpyrimido[4,5-b]quinoline-2,4(3H,10H)-dione (TPAdFlPh), and investigated their photophysical properties and performance as sensitizers in the photodehalogenation of aryl halides. We showed that the photophysical properties are significantly improved in these dFLs. The absorption bands of dFLs are redshifted and the absorbance is more than double that of riboflavin tetraacetate (RFTA). The singlet oxygen quantum yields of TPAdFlMe, TPAdFlTF and TPAdFlPh are 0.42, 0.25 and 0.39, respectively, and the corresponding redox potentials are −1.75, −0.75 and −1.71 V vs. Ag/Ag⁺, respectively, comparable to known deazaflavin-based sensitizers. Originating from these properties, TPAdFlMe and TPAdFlPh are capable of sensitizing the full photodehalogenation of 0.038 mmol p-iodoanisole, and the yields of the photodehalogenation of 0.038 mmol p-bromoanisole are 67 and 69%, respectively. They also demonstrate exceptional performance in the photodehalogenation of halides of polycyclic aromatics with yields in the range of 73% for 1-benzhydryl-3-bromobenzene to 100% for 1-bromonapthalene in 18 h runs. The performance of TPAdFlMe and TPAdFlPh in photodehalogenation are already comparable to recently reported deazaflavin-based sensitizers, and we propose the transformation would proceed though the consecutive photo-induced electron transfer (conPET) mechanism with consecutive excitation of charged deazaflavin-based radicals under light irradiation as the key step to generating the aryl radicals, and the vital role of sensitizer-based radicals is further confirmed by mechanistic investigations. We expect the findings will help to design novel flavin-based triplet sensitizers for photoredox catalytic organic transformations. Full article

Lubricants are essential for water-based drilling fluids. Catechol-based lubricants provide improved lubrication performance owing to their strong adhesion ability through the formation of coordination bonds inspired by mussel adhesion. However, the conventional synthetic ester and amide lubricants suffer from loss of adhesive capability due to hydrolysis and autoxidation. Inspired by mussels and melanin biosynthesis, a biomimetic strategy was developed to synthesize a high-adhesion lubricant with good stability via thiol-quinone Michael addition to restore and stabilize the catechol moiety. Bisphenol A was oxidized to the corresponding quinone using 2-iodoxybenzoic acid. Subsequent Michael addition reaction with 1-octadecanethiol produced a thiol-functionalized lubricant containing catechol moieties and long alkyl chains through an S-catecholyl linkage. Biomimetic principles were incorporated into both the molecular structure and the synthetic route, emulating the structural and functional features of mussel adhesion and melanin biosynthesis. Octadecanethiol provided sulfur-containing extreme-pressure functionality and contributed to strong adsorption on metal surfaces. The molecular structure was confirmed by FTIR, ¹H NMR, and ¹³C NMR. The thiol-functionalized lubricant formed strong coordination with Fe³⁺ and Fe²⁺ ions across a wide pH range, with an apparent complexation stoichiometry of 1:1 and conditional stability constants of 4.09 and 5.02, respectively. Bis-coordination formed a cross-linking network. It exhibited good resistance toward autoxidation and thermal stability up to 350 °C. In bentonite-based drilling fluids, the extreme pressure lubrication coefficient and adhesion coefficient at a 1% addition were 0.06 and 0.07, respectively. The coefficient of friction and wear scar diameter were 0.09 and 0.63 mm, respectively. The increased contact angle confirmed strong adsorption of the lubricant on metal surfaces. The lubricant combined strong adhesion, high stability, and excellent compatibility with drilling fluids, highlighting its potential as an advanced biomimetic lubricant. This biomimetic thiol-quinone addition strategy provides an effective approach to overcome the instability of conventional catechol-based lubricants. Full article

6(5H)-phenanthridinone derivatives, as an important class of alkaloids, have broad application value in drug development and functional material synthesis. In this study, a nickel-catalyzed synthetic strategy was developed, using 2-bromobenzamide compounds as starting materials. Through an intermolecular cyclization reaction, a series of 6(5H)-phenanthridinone derivatives bearing amide substituents was efficiently constructed. The optimal reaction system was identified: Ni(acac)₂/Zn as the catalyst, PCy₃ as the ligand, toluene as the solvent, Cs₂CO₃ as the base, under an argon atmosphere at 150 °C for 12 h. The target products were obtained in yields up to 88%. Further substrate scope exploration demonstrated the excellent generality of this method, successfully synthesizing 21 derivatives with various substitution patterns, achieving yields ranging from 51% to 92%, and showing good compatibility with multiple functional groups such as alkyl, aryl, and heterocyclic moieties. Importantly, the reaction remained stable during gram-scale experiments, successfully yielding the desired compound at 85%. This work not only provides an approach for the precise construction of the 6(5H)-phenanthridinone framework but also opens an efficient pathway for the controlled synthesis of amide-substituted derivatives. Full article

Background: The escalating spread of drug-resistant bacteria is intensifying the antibiotic resistance crisis, necessitating the urgent development of novel antimicrobial agents to address the resulting high global mortality rates and significant socioeconomic burden. Objectives: This study aimed to aminate the C-6 position of β-carboline and investigate the antibacterial activity and mechanism of action of the derivatives. Results: For the first time, 16 derivatives with various nitrogen-containing moieties, including aliphatic- and phenyl-amino, imidazolium, pyridinium, and quinolinium, were synthesized via amination at the C-6 position of β-carboline. These compounds exhibited moderate to good activity against Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Bacillus subtilis, with minimum inhibitory concentration (MIC) values ranging from 1.56 to 100 μg/mL. The study reveals that elongating an alkyl chain, incorporating a cationic scaffold, and expanding a π-delocalized system can enhance antibacterial activity. The most potent derivative from each series was selected for further mechanistic investigation against MRSA. All studied compounds demonstrated low hemolytic activity and low cytotoxicity. Studies on the antibacterial mechanism indicated that the compounds exert their antibacterial effects by disrupting bacterial cell walls and membranes. Additionally, two of the compounds were found to potentially disrupt the secondary structure of DNA. All tested compounds exhibited antibiofilm activity. Conclusions: Our findings demonstrate that amination modification at the C-6 position of β-carboline can enhance antibacterial activity by disrupting the cell wall membranes and interacting with bacterial DNA. These results provide a basis for further optimization of antibacterial agents based on β-carboline. Full article

While many [FeFe]-hydrogenase biomimetics are effective proton-reduction catalysts, few are active for H₂ oxidation, and examples containing both a pendant amine group, able to act as a proton relay, and a second redox center, both essential features of the enzymes, are rare. Here we report the preparation and oxidation chemistry of two ferrocene-functionalized amino-diphosphines (PCNCP), (CH₂PR₂)₂NCH₂Fc (R = Ph (1), Cy (2)), and their ethylenedithiolate (edt) diiron complexes, [Fe₂(CO)₄(μ-edt){κ²-(R₂PCH₂)₂NCH₂Fc}] (R = Ph (3), Cy (4)). Their crystallographic characterization shows that PCNCP occupies an apical–basal position. CV responses are slightly R-dependent, showing for 3 and 4 in three separate oxidative processes assigned to successive one-electron oxidation of the diiron core (quasireversible), appended Fc (reversible), and the amine–diiron moiety (irreversible), as confirmed by IR and UV–Vis spectroelectrochemical studies supported by Density Functional Theory (DFT) and Time-dependent Density Functional Theory (TDDFT) calculations. The first oxidation results in a structural rearrangement of the Fe(PNP)(CO) unit and the formation of a semi-bridging carbonyl. Slow protonation of 3 with HBF₄∙Et₂O affords the corresponding N-protonated cation in acetone, whilst μ-hydride products dominate for both 3 and 4 in CD₂Cl₂. A preliminary H₂ oxidation study was carried out with 3, and while there was some evidence of activity, it was much lower than reported for alkyl-functionalized PCNPC diiron derivatives. Full article

Background: Phenothiazine derivatives bearing trifluoromethyl substituents have attracted increasing interest as multifunctional scaffolds in drug repositioning strategies, particularly in cancer and infectious diseases. Structural modification of classical phenothiazines by incorporation of a quinoline moiety has previously been shown to enhance biological activity. Objectives: The present study aimed to develop an efficient synthesis of 8-trifluoromethylquinobenzothiazines and to evaluate the anticancer and antibacterial potential of their N-substituted analogues inspired by triflupromazine, trifluoperazine, and fluphenazine. Methods: 6H-8-Trifluoromethylquinobenzothiazine was synthesized by cyclization of 2-amino-4-trifluoromethylbenzenethiol and 3-bromo-2-chloroquinoline. The resulting quinobenzothiazine, unsubstituted at the nitrogen atom, was subjected to N-alkylation reactions to afford eleven new 6-dialkylaminoalkyl derivatives. Structural elucidation was performed using NMR and HRMS techniques. Anticancer activity was evaluated by MTT assay against human breast (MDA-MB-231), pancreatic (Mia-PaCa-2), and lung (A-549) carcinoma cell lines, as well as normal HaCaT keratinocytes. Antibacterial activity was assessed by MIC/MBC determination against selected Gram-positive and Gram-negative reference strains and clinical isolates. Results: Among the synthesized compounds, derivatives 8 and 12 exhibited the most favorable anticancer profiles, showing micromolar cytotoxicity (IC₅₀ ≈ 4–10 µM) against lung and pancreatic cancer cells combined with moderate selectivity toward cancer cells over normal keratinocytes. Compound 6 displayed lower cytotoxic potency but a notably high selectivity index due to minimal toxicity toward normal cells. In antibacterial assays, compound 3 exhibited activity against Gram-positive bacteria, including a methicillin-resistant Staphylococcus aureus isolate, with MIC values ranging from 7.8 to 15.6 µg/mL. The corresponding MBC values were equal to or twofold higher than the MICs (MBC/MIC = 1–2), fulfilling commonly accepted criteria for bactericidal activity (MBC/MIC ≤ 4). OD-based growth kinetics confirmed concentration-dependent inhibition of S. aureus growth. Conclusions: The obtained results identify 8-trifluoromethylquinobenzothiazines as a promising class of multifunctional compounds. Selected derivatives combine anticancer activity with acceptable selectivity or display potent antibacterial effects against clinically relevant Gram-positive pathogens. Full article

Proton exchange membranes (PEMs) are essential for fuel cells, yet conventional materials like Nafion suffer from humidity dependence and limited thermal stability. This study introduces sulfonated phenylene-bridged periodic mesoporous organosilicas (PMOs) as promising inorganic–organic hybrid PEMs, synthesized via surfactant-templating with varying alkyl chain lengths for different mesopore sizes. Post-synthetic functionalization involves nitration of phenylene moieties, reduction to amines, and ring-opening of propane or butane sultones to graft sulfonic acid groups via flexible spacers, achieving homogeneous distribution along pore walls. Post-functionalization is confirmed by powder X-ray diffraction (PXRD), revealing preserved 2D hexagonal p6mm ordering and phenylene stacking. N₂ physisorption shows type IV isotherms with reduced pore volumes and pore sizes. ¹H NMR is used to quantify functionalization degrees. Impedance spectroscopy on pressed pellets demonstrates proton conductivities up to 2 × 10⁻³ S cm⁻¹ at 30 °C and 90% RH, depending on the functionalization degree, confirming sulfonic acid-mediated conduction. Full article

The synthesis, phase behavior and semiconductor properties of two novel organosilicon tetramers with dialkyl-substituted [1]benzothieno[3,2-b]benzothiophene (BTBT) moieties, D4-Und-BTBT-Hex and D4-Hex-BTBT-Oct, are described. The synthesis of these molecules was carried out by sequential modification of the BTBT core by carbonyl-containing functional alkyl substituents using the Friedel–Crafts reaction, followed by the reduction in the keto group. The target tetramers, D4-Und-BTBT-Hex and D4-Hex-BTBT-Oct, were obtained by the hydrosilylation reaction between tetraallylsilane and corresponding 1,1,3,3-tetramethyl-1-(ω-(7-alkyl[1]benzothieno[3,2-b]benzothiophen-2-yl)alkyl)disiloxanes. The chemical structure of the compounds obtained was confirmed by NMR ¹H-, ¹³C- and ²⁹Si-spectroscopy, gel permeation chromatography and elemental analysis. Their phase behavior was investigated by differential scanning calorimetry, polarization optical microscopy and X-ray diffraction analysis. It was found that D4-Und-BTBT-Hex shows higher crystallinity at room temperature as compared to D4-Hex-BTBT-Oct, while both molecules possess smectic ordering favorable for active layer formation in organic field-effect transistors (OFETs). The active layers were applied by spin-coating under conditions of a homogeneous thin layer formation with a low content of defects. The devices obtained from D4-Und-BTBT-Hex have demonstrated good semiconductor characteristics in OFETs with a hole mobility up to 3.5 × 10⁻² cm² V⁻¹ s⁻¹, a low threshold voltage and an on/off ratio up to 10⁷. Full article

This study reports the solvent-free mechanochemical synthesis of a novel series of 2-hydrazone-bridged benzothiazole derivatives 19–52 via the reaction of 2-hydrazinylbenzothiazole derivatives 4–6 with O-alkylated benzaldehydes 7–18. The stereostructure of the E-isomers was confirmed by 2D NOESY spectroscopy. The antiproliferative potential of these newly prepared 2-hydrazone derivatives of benzothiazole 19–52 was evaluated in vitro against eight human cancer cell lines. Several compounds demonstrated low micromolar IC₅₀ values, with some outperforming the reference drug etoposide. Among the most potent compounds, the 6-chloro-2-hydrazone(3-fluorophenyl)benzothiazole derivative 38 exhibited remarkable activity against pancreatic adenocarcinoma (Capan-1, IC₅₀ = 0.6 µM) and non-small cell lung cancer (NCI-H460, IC₅₀ = 0.9 µM). Structure–activity relationship analysis revealed that derivatives 45–52, featuring a methoxy group at position 6 of the benzothiazole ring and either a methoxy or fluorine substituent at position 3 of the phenyl ring, showed consistently strong antiproliferative effects across all tested cell lines (IC₅₀ = 1.3–12.8 µM). Furthermore, compounds bearing N,N-diethylamino or N,N-dimethylamino groups at position 4 of the phenyl ring generally exhibited superior activity compared to those with morpholine or piperidine moieties. However, as this study represents an initial screening, further mechanistic investigations are required to confirm specific anticancer pathways and therapeutic relevance. In addition to their in vitro anticancer properties, the antibacterial activity of the compounds was assessed against both Gram-positive and Gram-negative bacteria. Notably, compound 37 demonstrated selective antibacterial activity against Pseudomonas aeruginosa (MIC = 4 µg/mL). Overall, this work highlights the efficiency of a green, mechanochemical approach for synthesizing E-isomer hydrazone-bridged benzothiazoles and underscores their potential as promising scaffolds for the development of potent antiproliferative agents. Full article