Understanding the activation mechanism of water molecules is of fundamental importance for catalytic water dissociation via water splitting. In this study, we employed first-principles molecular dynamics simulations to investigate the catalytic dissociation of H2O on 88 alloy clusters. Our results reveal that a larger red shift in the center of the coupled ν1 and ν3 stretching modes of adsorbed H2O correlates with a lower dissociation temperature. We observe an empirical correlation suggesting that dissociation is facilitated when the adsorption energy is comparable in magnitude to the HOMO–LUMO gap, which we propose as a hypothesis warranting further investigation with excited-state methods. Furthermore, comparison of the frontier molecular orbitals between precursor and intermediate states demonstrates that the number of frontier orbitals exhibiting increased overlap with the dissociating H atom is inversely correlated with the dissociation temperature. These findings provide atomic-scale insights into the activation mechanism of water dissociation on isolated gas-phase clusters and establish spectroscopic descriptors for evaluating the intrinsic reactivity of such model systems. We caution that extension of these findings to practical catalytic water splitting would require consideration of additional factors such as catalyst supports, solvents, and realistic reaction conditions.
The quinazoline/quinazolinone ring is known as a unique scaffold, and its derivatives possess a broad biological activity profile, including antibacterial, antifungal, anticonvulsant, anti-inflammatory, anti-HIV, and analgesic activity, primarily focusing on anticancer activity. In this study, the synthesis of 2-[[4-oxo-3-(substituted phenyl)-3,4-dihydro-(substituted quinazolin-2-yl)]thio]-N′-(aryl/heteroaryl methylene)acetohydrazide (4a–4x) derivatives and their potential anticancer activities were investigated on the lung cancer A549 cell line, the breast cancer MCF-7 cell line, and healthy fibroblast L929 cell line. Compounds 4c, 4i, 4m, and 4u were identified as the most cytotoxic and selective molecules on the A549 cell line (IC50: 44.75–78.13 µM), while 4i, 4l, 4m, and 4u were identified as the most cytotoxic and selective molecules on the MCF-7 cell line (IC50: 14.43–29.39 µM). The mechanisms of action of their anticancer activities were examined and studied. It was determined that these compounds induced strong apoptosis and significantly activated caspase-3 activation in both cell types and that they interrupted the cell cycle in the pre-G (sub G0) phase. Compounds 4m and 4u exhibited EGFR inhibition (IC50: 4.80 µM, IC50: 5.40 µM, respectively) at a level similar to the standard drug gefitinib (IC50: 1.86 ± 0.43 µM). Based on the results of the biological activity assays, molecular docking, and molecular dynamics simulation studies, the 4-quinazolinone–acetyl hydrazone scaffold can be considered a promising structural framework with potential anticancer activity. More specifically, the findings of this study indicate that the acetyl moiety may function as an important pharmacophoric group, while the trisubstituted quinazolinone core may represent a favorable structural feature for caspase-3 activation. However, the same structural framework appears to be less favorable for EGFR inhibition, possibly due to steric constraints within the EGFR binding pockets.
Acetohydroxyacid synthase (AHAS, EC 2.2.1.6) is a core enzymatic target in agrochemical research for herbicide development and has been widely investigated in recent decades. To develop novel AHAS-targeted herbicides, twenty-three acylthiourea derivatives were synthesized via fragment recombination and bioisosteric replacement strategies in this work. All target compounds were fully characterized by elemental analysis, mass spectrometry, FTIR spectroscopy, and 1H NMR spectroscopy. Dose–response trends from the Petri dish assay at 1, 10, and 100 mg L-1 show that root-growth inhibition increased synchronously with concentration. Preliminary bioassays across gradient concentrations (1, 10, 100 mg L−1) revealed dose-dependent growth-inhibitory effects of several derivatives against the monocot weed Digitaria adscendens and dicot weed Amaranthus retroflexus. At 100 mg/L pre-emergence treatment, compounds 4v (76.48 ± 1.47%), 4m (69.34 ± 1.62%), and 4l (67.77 ± 1.87%) exhibited the strongest inhibitory activity, comparable to or exceeding bensulfuron-methyl (70.41 ± 1.21%). All synthesized acylthiourea derivatives exhibited less than 20% growth inhibition toward wheat and soybean, demonstrating acceptable crop selectivity. In vivo enzymatic assays at 100 mg L−1 showed that 4l, 4m, and 4v achieved AHAS inhibition rates of 38.25 ± 1.81%, 35.74 ± 1.35%, and 38.75 ± 1.93%, comparable to or marginally exceeding that of bensulfuron-methyl (35.64 ± 1.40%). Molecular docking simulations yielded binding energies of −6.67 kcal mol−1 (4l), −6.29 kcal mol−1 (4m), and −6.90 kcal mol−1 (4v), all more favorable than −5.86 kcal mol−1 calculated for bensulfuron-methyl, indicating stronger target-enzyme binding affinity for these three compounds. This research suggests that these acylthiourea derivatives may serve as preliminary lead scaffolds for developing novel AHAS inhibitors via subsequent structural derivatization, pending further dose–response, mechanistic, and field-efficacy validation.
Biosurfactants are environmentally friendly surface-active compounds with promising applications in environmental remediation. In this study, a biosurfactant-producing bacterium, Bacillus (B.) velezensis SHB.28, was isolated from heavy metal-contaminated soil and evaluated for its ability to produce biosurfactants using date syrup as a low-cost agro-industrial substrate. Screening assays including drop-collapse (DC), oil spreading (OS), and emulsification index after 24 h E24 (%) confirmed strong biosurfactant production. Culture conditions were optimized, revealing that 30 °C, pH 6, and a C/N ratio between 10% and 20% provided optimal production. Under optimized conditions, the crude biosurfactant extract yield reached 2.16 g/L within 24 h, accompanied by a reduction in surface tension from 69 to 29.1 dyn/cm and high emulsification activity. Kinetic modeling showed that emulsification activity followed an exponential growth model (R2 = 0.985), whereas surface tension dynamics were well described by a spike decay–plateau model (R2 = 0.998). Structural characterization using Fourier-transform infrared spectroscopy (FTIR), electrospray ionization–mass spectrometry (ESI–MS), and nuclear magnetic resonance (NMR) spectroscopy revealed that the biosurfactants are surfactin- and iturin-like cyclic lipopeptides composed of a β-hydroxy fatty acid chain (C13–C15) linked to a cyclic peptide moiety. The biosurfactant exhibited a critical micelle concentration of 100 mg/L and an anionic character with a pHpzc of 5.7. Furthermore, it demonstrated high efficiency in removing heavy metals, achieving removal efficiencies of 99.88% for Fe2+, 99.69% for Pb2+, and 94.72% for Cu2+, outperforming conventional surfactants such as SDS and Tween 80. These findings highlight the potential of date syrup-derived surfactin and iturin from B. velezensis SHB.28 as sustainable and efficient biosurfactants for environmental remediation and heavy metal removal applications.
A magnetite–eggshell nanocomposite (Fe3O4@eggshell NC) was synthesized by green coprecipitation and evaluated for Cr(VI) removal from water. Passiflora ligularis peel extract, evaluated using a 23 factorial design, served as the biogenic medium, while eggshell waste acted as the support. Characterization included X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), scanning and transmission electron microscopy (SEM and TEM), Brunauer–Emmett–Teller (BET) analysis, zeta potential measurements, thermogravimetric analysis (TGA), vibrating sample magnetometry (VSM), and Mössbauer spectroscopy. The NC preserved Fe3O4 and CaCO3 crystalline phases, contained nanoparticles averaging 18 nm, and exhibited oxygenated surface functionalities, a BET surface area of 134.93 m2/g, amphoteric behavior, and a predominantly superparamagnetic response suitable for magnetic recovery. Under conditions of pH 4, 180 rpm, 60 min, 0.15 g NC, and 50 mg/L Cr(VI), removal reached 75.98%. Kinetic data followed the pseudo-first-order model, whereas equilibrium data were well described by the Sips isotherm, with an estimated capacity of 50.81 mg/g. At the investigated initial concentration of 50 mg/L, adsorption was exothermic and favored at temperatures up to 308 K, and the material retained moderate reusability during the first three alkaline-regeneration cycles. Overall, Fe3O4@eggshell NC is a waste-derived, magnetically recoverable adsorbent with favorable Cr(VI) uptake under moderately acidic conditions.
A series of novel substituted derivatives of the closo-decaborate anion [B10H10]2− bearing alkoxy spacer chains of varying length derived from ring-opened crown ethers (12-crown-4, 15-crown-5, and 18-crown-6) with pendant L-amino acid methyl ester residues (L-tryptophan and L-histidine) have been synthesized. The synthetic approach involved the nucleophilic ring-opening of oxonium crown ether derivatives of the closo-decaborate anion followed by coupling with amino acid methyl esters via mixed anhydride activation. The obtained compounds were characterized by multinuclear NMR spectroscopy (1H, 11B, 13C), IR spectroscopy, elemental analysis, and electrospray ionization mass spectrometry (ESI-MS). The compounds were obtained as sodium salts and evaluated for their in vitro cytotoxic and antiviral properties against the influenza A virus strain A/Moscow/78/2020 (H1N1)pdm09, which contains the S31N mutation conferring resistance to adamantane-class drugs. Cytotoxicity was assessed on MDCK cells, and antiviral activity was determined by cell ELISA. The results revealed a clear structure–activity relationship: the length of the alkoxy spacer chain significantly influenced both antiviral activity and selectivity. The shortest spacer (derived from 12-crown-4) proved to be optimal, while elongation of the chain led to a decrease in antiviral potency. The compound containing a 12-crown-4-derived spacer and a tryptophan methyl ester residue exhibited the highest selectivity index (SI = 155) with low cytotoxicity (CC50 = 155 µg/mL) and high antiviral activity (IC50 = 1.0 µg/mL). Tryptophan-containing derivatives consistently outperformed their histidine analogues, confirming the key role of the indole side chain in antiviral activity. Overall, the closo-decaborate platform with crown ether-derived spacers and amino acid ester pendant groups represents a promising scaffold for the development of low-toxicity, highly selective inhibitors of influenza A virus replication. The compound with the 12-crown-4-derived spacer and a tryptophan methyl ester residue merits further investigation as the most promising among the synthesized samples.
Diabetes mellitus is a long-term metabolic disease associated with elevated glucose levels in blood and still constitutes one of the major public health issues worldwide. Inhibition of carbohydrate-digesting enzymes like α-amylase and α-glucosidase has been found to be effective in controlling postprandial hyperglycemia. The current study focused on designing, synthesis, characterization, and evaluation of novel 2,4-thiazolidinedione derivatives (D1–D5) as potent antidiabetic drugs utilizing combined in silico, in vitro, and in vivo techniques. Results from drug-likeness and ADME analyses indicated that all synthesized derivatives met Lipinski’s rule of five and had desirable pharmacokinetics properties along with reduced toxicity. Molecular docking against maltase-glucoamylase (human; PDB ID: 3TOP) protein showed good binding affinities of both D1 and D5 derivatives (−7.74 and −7.40 kcal/mol respectively) due to stable interactions with catalytic residues of enzymes. Inhibition of enzymes in vitro showed that D1 and D5 had the highest inhibitory activities of all synthesized derivatives, with IC50 of 33.86 ± 2.1 and 37.55 ± 1.7 μM against α-amylase and 29.81 ± 3.2 and 32.43 ± 1.2 μM against α-glucosidase, respectively. Cytocompatibility tests on L6 myoblast cells proved that the lead compounds were well tolerated. In addition, studies in a model of Drosophila melanogaster induced by a high-sugar diet revealed a significant decrease in the level of glucose concentration depending on the dose, especially for D1 and D5, indicating their antihyperglycemic activity in vivo. Thus, these data confirm that D1 and D5 can be regarded as promising lead compounds for the development of new antidiabetics acting via inhibition of carbohydrate-metabolizing enzymes.
Sodium metal anodes (SMAs) are regarded as the most promising anode materials for next-generation high-energy-density sodium metal batteries, owing to their ultrahigh theoretical specific capacity (1166 mAh g−1) and low electrochemical potential (−2.71 V vs. SHEs). However, their practical application is severely hindered by a series of interrelated challenges, including unstable solid electrolyte interphase (SEI) films, severe volume fluctuations arising from their hostless nature, uncontrollable dendrite growth, and the consequent low Coulombic efficiency and short cycle life. This review systematically summarizes recent progress in stabilizing SMAs through three major categories of strategies: current collector engineering, which involves the design of planar, three-dimensional, and gradient architectures to regulate the local current density and Na+ flux, thereby guiding uniform nucleation and enabling “bottom-up” dendrite-free deposition; electrolyte engineering, which focuses on optimizing solvents, salts, and functional additives to tailor the solvation structure, construct robust inorganic-rich SEI layers, and utilize electrostatic shielding effects to suppress dendrite formation; and artificial SEI engineering, which aims to pre-construct inorganic or inorganic–organic hybrid protective layers that establish a physicochemical barrier between the electrode and electrolyte, combining high ionic conductivity, superior mechanical strength, and sufficient flexibility. Finally, we provide a critical perspective on the remaining challenges and outline future research directions, emphasizing the importance of in situ/operando characterization, synergistic multi-strategy integration, breakthroughs in high areal capacity and high-rate performance, and artificial intelligence-driven material discovery for the practical implementation of SMAs.
Stress-induced sebaceous hyperactivity is a key driver of acne and seborrheic dermatitis; however, research investigating the pathway-specific mechanisms through which stress exerts its effects and the suppression of sebum production via targeting stress signaling remains relatively limited. In this study, we investigated whether Camellia nitidissima flower extract (CNF) could counteract stress-induced sebaceous dysfunction and its underlying mechanisms. Using a cortisone-stimulated SZ95 human sebocyte model, we evaluated lipid accumulation, cortisol production, signaling pathway activation, and apoptotic markers. CNF treatment dose-dependently suppressed cortisone-induced lipid production, reducing triglyceride, cholesterol, and free fatty acid levels by up to 35.44%, 38.02%, and 46.39%. Mechanistically, CNF inhibited 11β-HSD1 expression (17.17% reduction) and cortisol secretion (32.84% decrease), thereby blocking local cortisol reactivation. This upstream interception subsequently attenuated PI3K/Akt/mTOR hyperphosphorylation, downregulated lipogenic transcription factors (SREBP-1, PPARγ, LXRα, C/EBP-α) and their target enzymes (FAS, ACC, DGAT). Beyond lipid synthesis inhibition, CNF reversed cortisone-induced apoptosis resistance by reducing the Bcl-2/Bax ratio and suppressing PCNA-mediated hyperproliferation, thereby decreasing sebocyte number. These findings demonstrate that CNF exerts dual oil-control effects: reducing lipid production per cell and reducing lipid-producing cell abundance. Collectively, CNF represents a promising multi-target botanical agent for managing stress-related sebaceous disorders and cosmetic sebum regulation.
Lyme borreliosis (LB) is a tick-borne disease caused by a diverse and expanding group of spirochetes characterized by complex biology and advanced immune evasion mechanisms. It presents a wide range of clinical symptoms affecting multiple organ systems and can lead to persistent complications. The pathogenesis of LB remains incompletely understood, and diagnosis typically relies on serologic assays to detect antibodies against LB. However, the standard two-tiered testing (STTT) algorithm is limited by cross-reactivity, low sensitivity, and delayed results, hindering timely and accurate diagnosis. Although molecular tests are considered the gold standard, their reliance on centralized laboratories can delay critical treatment decisions. This underscores the urgent need for rapid, reliable diagnostic tools, particularly for use at the point of hospital admission. Point-of-care serological and direct antigen testing can provide actionable information, supporting decentralized healthcare systems in diagnosing complex diseases, such as LB. In this study, we developed two fluorescent polarization immunoassays (FPIAs) using IgM and IgG LB-specific synthetic epitopes/peptides to evaluate their diagnostic potential. These FPIAs showed high sensitivity and specificity in detecting IgM or IgG anti-LB antibodies in patient sera within minutes. The fluorescently labeled synthetic peptides produced significant polarization differences between infected and healthy samples, allowing clear discrimination. The FPIA-LB functions as a one-step assay, eliminating the need for secondary antibodies or complex protocols. This work highlights the FPIA technique as a robust, rapid, and efficient tool for LB diagnosis, offering a promising advance in improving early detection and patient outcomes, which could save lives and reduce long-term health complications.
Betanin is the main betacyanin and major pigment extracted from red beets (Beta vulgaris). While its applications as food colorant, color-based sensors, antioxidant, anti-inflammatory, and antimicrobial traits are well-known, this natural dye is underestimated and underexploited in the field of light- and electric-responsive materials and devices. This comprehensive review describes the optical properties and molecular orbitals of this chromophore, along with its excited-state relaxation dynamics and emission quantum yields. Other relevant and basic behaviors of its excited-state features, such as cis-trans-photoisomerization, singlet–singlet energy transfer, photo-induced electron transfer, photosensitization of 1O2, and relative photo-instability are also presented in some relevant details. Photoconductive materials based on betanin and their related devices such as organic light emitting diodes, and dye-sensitized solar cells, are also surveyed. Other visible light-driven processes such as photodynamic processes and heterogeneous catalysis based on betanin-containing assembly/composites are demonstrated. Finally, the use of betanin as nonlinear optical materials is addressed.
Na4Fe3(PO4)2P2O7 (NFPP), an iron-based mixed phosphate–pyrophosphate cathode material, has emerged as one of the most commercially promising candidates for large-scale sodium-ion battery (SIB) energy storage applications. Its exceptional characteristics—an ultralow volume change of less than 4% during Na+ de/intercalation, a three-dimensional open framework enabling rapid ionic diffusion, and the use of earth-abundant, low-cost iron as the redox center—collectively deliver a unique combination of structural stability, rate capability, and economic viability. However, the fundamental challenge of phase-purity control, arising from the three-phase thermodynamic competition among NFPP, electrochemically inert maricite-NaFePO4, and Na2FeP2O7 during synthesis, critically limits its electrochemical performance. This review provides a systematic overview of NFPP research progress from 2012 to 2026, covering crystal structure and sodium storage mechanisms, synthesis methodologies, and—most critically—Phase Adjustment and modification strategies including non-stoichiometric regulation, defect engineering, elemental doping, anionic substitution, and heterostructure design. Mechanistic insights into how each strategy addresses the phase-purity challenge and enhances electrochemical kinetics are critically examined. Industrialization progress, full-cell performance evaluation, cost analysis, and future research directions toward practical deployment are also discussed.
A series of boron-functionalised exo-norbornene monomers bearing boronic ester groups were synthesised via a condensation reaction and subsequently polymerised through ring-opening metathesis polymerisation (ROMP) to afford well-defined poly(norbornene-B-arylene-dioxaborepine)s. The incorporation of Lewis acidic boron centres into the norbornene-derived polymer backbone enables access to coordination-active macromolecular systems with tuneable interactions towards nucleophilic species. The resulting polymers demonstrate enhanced structural definition and stability, thereby confirming the robustness of the synthetic approach and the successful incorporation of boron functionalities into ROMP-derived architectures. This work establishes a general and efficient strategy for the preparation of boron-containing ROMP polymers, providing a versatile platform for the development of coordination-responsive polymeric materials.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) deposition and cognitive decline. Clinical evidence indicates that Hericium erinaceus whole fruiting body powder offers limited therapeutic efficacy, which is suggested to be constrained by whole-food matrix interference and uncertainties in central nervous system (CNS) exposure. Therefore, we hypothesized that erinacine C (EC)—a purified active component from Hericium erinaceus mycelia—could resolve these limitations and potentially exhibit favorable neuroprotective effects owing to its low molecular weight and lipophilicity. In this study, we investigated the neuroprotective potential and associated signaling alterations of EC using APP/PS1 transgenic mice and Aβ25-35-induced PC12 cells. In vivo, oral administration of EC alleviated deficits in activities of daily living, as evidenced by improvements in nesting and burrowing behaviors, along with enhanced short-term spatial memory in the Y-maze test. EC treatment was associated with a reduction in hippocampal Aβ plaque accumulation, suppression of glial activation (GFAP and IBA1), and decreased IL-6 levels in both serum and hippocampal tissues. In vitro, EC intervention counteracted Aβ25-35-induced cytotoxicity in PC12 cells. Analysis of signaling markers revealed that EC treatment was accompanied by a restoration of p-Akt/Akt levels and a suppression of p-GSK3β (Tyr216) activation. Consequently, EC treatment was correlated with reduced tau hyperphosphorylation, the up-regulation of the anti-apoptotic protein Bcl-2, and the down-regulation of pro-apoptotic markers including Bax and cleaved-caspase-3, thereby lowering the total apoptotic rate. Taken together, these findings suggest that EC may mitigate cognitive impairment and neurodegeneration in parallel with alterations in the Akt/GSK3β/tau/caspase-3 signaling response, thereby representing a potentially promising therapeutic candidate for the intervention of AD.
Colorectal cancer (CRC) is the second leading cause of cancer-associated mortality and accounts for ~10% of all cancer cases. Global CRC cases were estimated at 1.9 million and 930,000 deaths in 2022. Despite improved access to CRC screening and treatment, death rates are expected to drastically increase in low-resource areas, highlighting an urgent need for innovative CRC treatment interventions. Current chemotherapy presents challenges, such as poor bioavailability, multidrug resistance, and adverse bystander effects. Therefore, it is imperative to develop new and CRC-specific therapeutic strategies. Targeted therapy has significantly improved drug delivery and efficacy in the treatment of various diseases, including cancer. Although several preclinical studies are currently ongoing in cancer therapy, there is a paucity of information about targeted CRC treatment. Hence, this review highlights the promising role of aptamer- and gold nanoparticles (AuNPs)-based systems for targeted CRC treatment. This strategy leverages the unique properties of aptamers and AuNPs as drug carriers, targeting and therapeutic agents. Overall, aptamers in combination with AuNPs are projected to improve the delivery of chemotherapeutics to CRC cells. However, further studies are warranted to validate the biodistribution and safety profile of aptamer- and AuNPs-based systems as potential tools for CRC treatment.
Small gases pose an unusual problem for studies of molecular transport in proteins. O2, CO, H2, and NO can cross short-lived internal spaces opened by protein fluctuations, often faster than experiments can follow continuous migration. Time-resolved crystallography can localize sufficiently populated intermediates, whereas spectroscopy, isotope exchange, and kinetic measurements report molecular exchange over their respective timescales without resolving the complete route. Pressurized noble-gas structures expose internal accommodation sites but rely on surrogate molecules whose size and interactions differ from those of physiological gases. Geometry-based tunnel searches identify available space, while molecular dynamics follows explicit movement through a fluctuating protein. Free-energy and enhanced-sampling approaches can access states or transitions that remain undersampled in direct trajectories. These techniques resolve different quantities rather than progressively more accurate estimates of gas transport. In this Perspective, we argue that gas-migration pathways should be evaluated by the physical consistency of independent observables, with each method interpreted according to the quantity it resolves. This distinction explains why a cavity visible crystallographically may not carry substantial flux, why a rapidly crossed route can remain structurally inconspicuous, and why static narrowing can alter diffusion without predicting its magnitude. Agreement among methods can support a transport assignment when the quantities they resolve are physically consistent with the same mechanism; apparent disagreement may instead reflect differences among occupancy, accessibility, residence, energetic preference, and molecular traffic.
The pyranoside-into-furanoside (PIF) rearrangement is an uncommon but important process in carbohydrate chemistry. The quantum chemical investigation of the driving force of the recently discovered TfOH-catalyzed ring contraction revealed that it stemmed from the π–π interactions of the phenyl rings in benzoyl-protecting groups. In this study, we focused on the kinetic aspects, which included preliminary 2-O-benzoyl group rotation followed by the protonation of the endo-cyclic O5 atom. Using a combination of DFT and DLPNO-CCSDT methods, we found that in some cases, DFT may not produce adequate energies at the rate-limiting stage of the pyranoside ring opening, presumably due to inadequate modeling of Van der Waals interactions. Predicted rate constants for the PIF rearrangement of the β-O-methyl and β-S-ethyl galactosides were in agreement with NMR kinetic experiments, as the latter reacts significantly slower. The estimated constant for the β-O-phenyl galactoside supports its inability to undergo ring contraction and suggests temperatures of over 400 K for such transformation. The proposed mechanism was additionally confirmed by substituting the triflic acid with the much weaker trifluoroacetic one, which led to a drastic decrease of the reaction rate both in computations and in the experiment.
A series of N-phenyl-3-(thiophen-2-yl)acrylamide derivatives were designed and synthesized to investigate the influence of electronic and steric modifications on cytotoxic activity. Although related thiophene-containing acrylamides have been reported, the specific compounds studied in this study have not been previously described. Structural variations were introduced at the para position of the N-phenyl ring (H, CF3, and OCF3) and at the 5-position of the thiophene ring (H and CH3) to enable preliminary structure–activity relationship (SAR) analysis. The target compounds were synthesized via Knoevenagel–Doebner condensation, followed by carbodiimide-mediated amide coupling. The compounds were characterized using nuclear magnetic resonance (NMR) spectroscopy, high-resolution mass spectrometry (HRMS), Fourier-transform infrared (FTIR) spectroscopy, and high-performance liquid chromatography (HPLC). Computational evaluation indicated compliance with Lipinski’s rule of five and the absence of predicted mutagenic, tumorigenic, irritant, and reproductive risks. Cytotoxic activity was determined using the sulforhodamine B (SRB) assay against human breast adenocarcinoma (MCF-7), gastric adenocarcinoma (AGS), colorectal adenocarcinoma (Caco-2), oral squamous cell carcinoma (HSC-3), hepatocellular carcinoma (HepG2) cell lines and non-cancerous human dermal fibroblasts (HDF). Compounds 11 and 16 displayed the most consistent activity, with half-maximal inhibitory concentration (IC50) values of 379, 420, and 265 μM and 272, 256, and 242 μM against AGS, Caco-2, and MCF-7 cells, respectively. MCF-7 cells were the most sensitive model. The most active derivative was compound 16, suggesting that the combination of a 5-methylthiophene moiety and a para-CF3 substituent may be beneficial within this limited compound series. These findings provide a preliminary evaluation of this scaffold and will help guide future studies on structural modifications.
This review provides a comprehensive analysis of Ylang-Ylang (Cananga odorata) essential oil (YYEO), describing its botany, historical evolution, and global commercial significance. It systematically provides information on traditional extraction techniques such as hydrodistillation, steam distillation, and solvent extraction alongside innovative green technologies, including microwave-assisted distillation (MAD), supercritical fluid extraction (SFE), and ultrasound-assisted extraction (UAE). Conventional distillation methods are compared with greener technologies. The reviewed studies indicate that microwave-assisted processing can reduce YYEO extraction time from approximately 19 h for conventional hydrodistillation to about 40 min while improving the retention of light oxygenated compounds. In particular, light oxygenated compounds have been reported at approximately 81.23% in solvent-free microwave extracts, compared with 69.94% for hydrodistillation and 57.98% for steam distillation. It has also been reported that YYEO contains more than 50 volatile secondary metabolites, with linalool representing about 28% of the oxygenated fraction, while sesquiterpene-rich hydrocarbons can account for up to 63% of the essential oil. The reviewed studies further demonstrate insecticidal, antimicrobial, antioxidant, anti-inflammatory, and neurobiological activities, supporting the potential use of YYEO in sustainable protective materials and health-related applications. Finally, emerging frontiers in protective smart textiles, living fabrics, and sustainable closed-loop manufacturing paradigms are discussed to outline future directions for bio-based material science.
