Chemistry and Materials Science

Abstract: Aspergillus nidulans, a model filamentous fungus endowed with well-established genetic tools and a repertoire of cryptic secondary metabolite biosynthetic gene clusters (BGCs), is extensively exploited as a microbial chassis for heterologous biosynthesis. Mining of its secondary metabolites facilitates the discovery of novel bioactive compounds and the development and application of chassis cells. In the course of heterologous expression of exogenous genes in A. nidulans, we unexpectedly observed the activation of cryptic host BGCs, which resulted in substantial alterations to its secondary metabolic profile. Four previously undescribed compounds (1–4), together with six known analogs (5–10), were isolated from three recombinant A. nidulans strains. Notably, compounds 1–3 are the first naturally occurring examples of diketopiperazine-isoindolinone hybrid alkaloids, while compound 4 is a previously unreported benzofuran carboxylic acid derivative. Their structures and absolute configurations were assigned by interpretation of a combination of spectroscopic data and electronic circular dichroism calculations. Compounds 4 and 5 exhibited potent DPPH radical scavenging activity (IC₅₀, 6.01 and 7.00 μg·mL^-1, respectively). This study uncovers a "metabolic perturbation" effect on the host metabolic network during heterologous expression and offers a new strategy for activating silent gene clusters and discovering novel natural products through genetic manipulation.

Abstract: Cosmetic preservatives should have reduced percutaneous absorption to lower the risk of systemic exposure and skin irritation. In this work, Escherichia coli β-galactosidase was used to enzymatically modify several of the commonly used cosmetic preservatives to produce their corresponding galactosylated derivatives: benzyl alcohol β-D-galactopyranoside 7, 2-phenoxyethanol β-D-galactopyranoside 8, chlorphenesin β-D-galactopyranoside 9, 1,2-hexanediol β-D-galactopyranoside 10, 1,2-octanediol β-D-galactopyranoside 11, and 2-phenylethyl β-D-galactopyranoside 12. HPLC and NMR spectroscopy were used to analyze the synthesized derivatives. The Franz diffusion cell assay was used to evaluate skin penetration. 2-phenoxyethanol (PE), chlorphenesin (CPN), and 2-phenylethanol (PhE), exhibited measurable skin penetration with flux values ranging from 3.82 to 7.34 µg·h⁻¹·cm⁻² and permeability coefficients (Kp) between 1.38 and 3.00 ×10⁻³ cm·h⁻¹. In contrast, their galactosylated derivatives showed markedly reduced permeation under the same experimental conditions. Moreover, brine shrimp lethality assays indicated that galactosylated derivatives had significantly higher LD₅₀ values (1.6–2.1 mg/mL) than their parent compounds (0.1–0.79 mg/mL), suggesting lower cytotoxicity. These findings suggest that enzymatic galactosylation can significantly decrease skin permeability and the toxicity of cosmetic preservatives, highlighting its potential as a strategy to improve the safety of cosmetic ingredients.

Abstract: Quantitative structure–activity relationship (QSAR) modeling has traditionally relied on expert-designed molecular descriptors to encode chemical structures. DeepSnap is a descriptor-free QSAR approach that converts three-dimensional molecular structures into image representations and feeds them directly into convolutional neural networks for activity prediction. The method generates a conformer for each molecule, renders it as a color-coded molecular image, and captures omnidirectional snapshots from systematically varied viewing angles. This review traces DeepSnap from its introduction in 2018 to its current state. The method has been applied to 35 nuclear receptor endpoints from the Tox21 10K library (mean AUC 0.884), 59 molecular initiating event models spanning the full Tox21 target panel, rat hepatic clearance (ensemble AUC 0.943), and blood–brain barrier penetration (ensemble AUC 0.936). An ensemble strategy combining image-based and descriptor-based predictions has consistently outperformed either approach alone. The computational pipeline has evolved from a DIGITS/Caffe/Jmol system to a TensorFlow/Keras/PyMOL framework. Limitations include endpoint-dependent parameter sensitivity, class imbalance effects, the absence of direct comparisons with graph neural networks, and an interpretability gap addressed in part by CAM-family visualization in the AI-SHIPS platform and S-COPHY. Future directions include systematic application of explainable AI methods, automated hyperparameter optimization, and integration with graph-based approaches.

Abstract: The development of new chronobiotics, substances capable of selectively modulating the parameters of circadian rhythms, is hampered by the fragmented nature and limited volume of available experimental data.In the present study, a comprehensive evaluation of the applicability of the SMILES-Transformer architecture to the classification of circadian rhythm modulators was performed using the specialised ChronobioticsDB resource, and the first systematic virtual screening of the SAVI (Synthetically Accessible Virtual Inventory) library of synthetically accessible compounds for chronobiotic activity was carried out. Rigorous protocols were applied for model training and validation: Data-Efficient Modeling (DEM) assessment with 20 repeats, repeated scaffold validation (5 × 5), and a comparative analysis of training strategies (feature-based vs. end-to-end fine-tuning). The influence of three variants of circadian-effect labelling (raw, aggregated, and expert-curated) and three loss functions (BCE, Focal Loss, and Asymmetric Loss) on the quality of multi-label classification was investigated. The results demonstrate that systematic hyperparameter optimisation in end-to-end mode provides the best predictive performance (ROC-AUC 0.666 for the effect_coarse task), whereas standard fine-tuning without optimisation leads to overfitting (ROC-AUC 0.470). Scaffold validation confirmed the ability of the model to generalise to structurally novel compounds (ROC-AUC 0.587). Expert aggregation of labels improved the recognition of rare classes (F1-macro 0.254 versus 0.148 for the raw labelling). Based on the trained models, a consensus virtual screening of the SAVI library was performed using four independent classifiers (classf, effect_coarse, target, mechanism). From more than five million compounds, 10,000 of the most promising candidates were selected, among which 34 super-candidates (consensus score > 0.9) and 435 strong candidates (> 0.8) were identified. Analysis of the predicted targets revealed dominance of the CLOCK-BMAL1 complex (60.49%), while among effects the circadian phase shift prevailed (37%). All identified candidates are synthetically accessible and are recommended for prioritised experimental verification.

Abstract: Oleoresins are complex natural lipophilic matrices traditionally analyzed using chromatographic techniques that require extensive sample preparation, derivatization, and authentic standards. Amazonian oleoresins from Copaifera and Eperua species (Fabaceae) represent valuable bioresources with recognized pharmacological potential, largely attributed to diterpenoids such as copalic and hardwickiic acids, as well as bioactive sesquiterpenes, including the cannabinoid b-caryophyllene. In this study, we present a proof-of-concept application of Direct Analysis in Real Time coupled with High-Resolution Mass Spectrometry (DART-HRMS) as a rapid, direct, and environmentally friendly approach for chemical fingerprinting and semi-targeted screening of the two most important amazonian oleoresins from these two genera: Eperua oleifera and Copaifera multijuga. Analyses were performed using a Q Exactive Orbitrap coupled to a DART ion source under after conditions optimization. Hardwickiic acid was used as a model compound for method optimization, with optimal performance achieved at 200 °C and 100 V, yielding stable signal intensities (CV < 10%) and high mass accuracy (< 1 ppm). The method enabled reproducible detection of diterpenic acids in both oleoresins, allowing differentiation of their chemical profiles and assessment of short-term stability under ambient conditions. In addition to diterpenes, free fatty acids were also detected, expanding the compositional characterization of these matrices. Compound annotation was performed based on accurate mass measurements and literature comparison, corresponding to Level 5 confidence according to established metabolomics criteria. Although the absence of chromatographic separation limits isomer discrimination and absolute quantification, DART-HRMS provides a rapid and solvent-free strategy for chemical fingerprinting and preliminary characterization of oleoresins. This approach aligns with Green Chemistry principles and shows strong potential as a screening and triage tool for quality control, chemotaxonomic studies, and sustainable valorization of Amazonian natural products.

Abstract: Oleanolic acid (OA) is a hydrophobic pentacyclic triterpene widely distributed in the plant kingdom and characterized by broad biological activity, including antioxidant, anti-inflammatory, neuroprotective, renoprotective, and anticancer effects. Increasing evidence suggests, however, that many of these actions are better explained not by single molecular targets, but by OA-dependent modulation of an integrated organelle stress network involving mitochondria, the endoplasmic reticulum (ER), autophagy, mitophagy, and apoptosis. This review critically analyzes the available evidence on the effects of OA on the mitochondria–ER–autophagy–apoptosis axis, with particular emphasis on mechanisms governing the transition between cellular adaptation and cell death. The available literature indicates that, in non-cancer models, OA most commonly lowers reactive oxygen species (ROS), stabilizes mitochondrial function, attenuates the ER stress signature, and promotes adaptive autophagy and mitophagy. In contrast, in many cancer models, OA may enhance mitochondrial dysfunction, lower the threshold for mitochondrial apoptosis, and induce autophagy that can be either protective or cytotoxic depending on the biological context. Overall, the current evidence supports a model in which OA acts as a context-dependent modulator of the organelle stress threshold rather than as a uniformly cytoprotective or uniformly proapoptotic compound. At the same time, the literature remains heterogeneous with respect to models, doses, exposure times, and markers used, while poor aqueous solubility and limited bioavailability continue to constrain translation. Future studies should therefore integrate analyses of mitochondria, ER, mitochondria–ER contact sites (MERCS), autophagy, apoptosis, pharmacokinetics, formulation, and safety in order to define the true potential of OA as a modulator of biological stress.

Abstract: Belonging to the Euphorbiaceae family, Jatropha genus is a promising source for discovering of antitumor compounds. Jatropha ribifolia is a traditionally used species in folk medicine in the semi-arid region of Brazil with a few chemical and pharmacological reports. Based on that, the aim of the current work is to isolate, structurally characterize, and assess the cytotoxic activity of isolated compounds through in vitro and in silico analyses. To achieve these main goals, the underground parts were dried, extracted and purified using classical and instrumental chromatographic techniques, leading to the isolation of 16 compounds. Altogether with HR-ESI-MS, IR, one- and two-dimensional NMR experiments, eight previously unreported diterpenes, named ribifolones A-H, along eight known compounds, were obtained and are herein described. Regarding their activity against melanoma (SK-MEL-28) and colorectal cancer (HCT-116) cell lines, jatrophone was the most potent with IC50 of 6.19 µM and 10.09 µM followed by ribifolone that exhibited a moderate cytotoxicity with IC₅₀ values of 50.71 µM and 33.39 µM, respectively. Network pharmacology analysis suggests the involvement of PI3K-AKT-mTor pathway in the activity of both compounds, meanwhile molecular docking and dynamics simulations demonstrate the main interactions with key proteins in the pathway and highlighted the estrogen receptor beta (ERβ) as putative target. This work opens new perspectives for the discovery of bioactive compounds found in Euphorbiaceae species, especially from those occurring in Caatinga.

Abstract: Alzheimer’s disease (AD) represents a escalating global neuropharmacological crisis, with prevalence in high-growth demographic regions such as India projected to exceed 14 million by 2040. This study addresses the urgent need for high-potency, dual-site acetylcholinesterase (AChE) inhibitors through an integrated computational pipeline. Background: We address the failure of mono-target paradigms by designing scaffolds capable of simultaneously anchoring the Catalytic Active Site (CAS) and the Peripheral Anionic Site (PAS). Methods: A robust GA-MLR QSAR model was developed from 115 quinoline analogues using 11,135 descriptors. Lead candidates were prioritized via blind molecular docking (7XN1) and 100-ns molecular dynamics (MD) simulations. Results: The five-descriptor model (R2 = 0.7569, QLOO2 = 0.7244) was validated by an external set of 8 experimental compounds (Rext2 = 0.8620). Lead Compound 19 emerged as a superior candidate (ΔG = -11.1 kcal/mol), exhibiting a stable MD trajectory (PL-RMSD ≈ 2.4 Å) and preserving essential Gly121-His447 catalytic anti-correlations. Conclusions: This study provides a statistically validated scaffold and mechanistic foundation for future biomimetic chromatography validation, advancing the high-throughput screening of neuroprotective agents on a global scale.

Abstract: Human African Trypanosomiasis (HAT) and malaria are serious infectious diseases endemic in tropical regions, caused by protozoan parasites, and necessitating an urgent development of new antiprotozoal drugs. As part of our ongoing search for new antiprotozoal steroidal alkaloids from plants, we investigated the methanolic stem bark extract of Holarrhena pubescens (Apocynaceae). H. pubescens is a tropical tree that some Kenyan coastal communities have long used to treat various ailments, including fever and stomach pain. The crude extract, alkaloid fraction, and 16 subfractions acquired through centrifugal partition chromatography (CPC) displayed promising in vitro antiprotozoal activity against Trypanosoma brucei rhodesiense (Tbr) and Plasmodium falciparum (Pf). Partial least squares (PLS) regression modelling of UHPLC/+ESI QqTOF-MS data and antiprotozoal activity data of the crude extract and its fractions was performed to predict compounds that may be responsible for the observed antiplasmodial activity. Chromatographic separation of the alkaloid fraction afforded one new steroidal alkaloid (5), along with 18 known compounds (1, 2, 4, 6–20), and one artifact (3) that was presumably formed during the acid-base extraction process. The structural characterization of the isolated compounds was accomplished using UHPLC/+ESI-QqTOF-MS/MS and NMR spectroscopy. The isolated compounds were tested for their in vitro antiprotozoal properties against the two aforementioned pathogens, as well as for their cytotoxicity against mammalian cells (L6 cell line). Compounds 2 and 16 (IC₅₀ = 0.2 μmol/L) demonstrated the highest antitrypanosomal activity, with compound 2 showing the highest selectivity (SI = 127). The new compound 5 exhibited the strongest antiplasmodial activity and selectivity against Pf (IC₅₀ = 0.7 μmol/L, SI = 43). Our findings provide further promising antiprotozoal leads for HAT and Malaria.

Abstract:

Many cannabinoids are derived from Cannabis and exhibit a diverse range of pharmacological properties. Predictions of bioactivities of these compounds were conducted by molecular docking computation on two transient receptor potential (TRP) receptors (TRPV1 and TRPC5) found on human glioma (U-87 MG) cells. These predictions were experimentally confirmed by monitoring changes in intracellular calcium concentration in U-87 MG cells treated with cannabinol (CBN), cannabichromene (CBC), and cannabicyclol (CBL), as measured using a fluorescence microplate reader. The results indicate that CBN and CBC are bioactive, whereas CBL exhibits minimal activity. These findings are consistent with predictions obtained from molecular docking computation based on AutoDock Vina.

Abstract: The c-Jun N-terminal kinase (JNK) signaling cascade is a central regulator of cellular stress responses and a validated therapeutic target for diverse pathologies, including neurodegeneration, fibrosis, and cancer. However, the development of direct JNK inhibitors has been impeded by challenges regarding isoform selectivity and on-target toxicity. Consequently, medicinal chemistry efforts have shifted upstream to the "gatekeepers" of the pathway: the dual-specificity kinases MKK4 and MKK7. This review provides a comprehensive analysis of the structural biology, physiological functions, and pharmacological inhibition of these critical signaling nodes. We highlight the non-redundant therapeutic potential of these kinases, contrasting the role of MKK4 inhibition in unlocking liver regeneration with the utility of MKK7 inhibition in suppressing fibrosis and chronic inflammation. A systematic overview of small-molecule inhibitors is presented. For MKK4, we discuss the evolution from early promiscuous chemotypes to the first-in-class clinical candidate HRX215, which has demonstrated safety and efficacy in promoting hepatocyte proliferation. For MKK7, we examine the design of covalent inhibitors exploiting the unique hinge-region cysteine (Cys218), as well as emerging modalities such as lysine-targeting binders and peptide inhibitors disrupting protein-protein interactions. Finally, we discuss remaining challenges and future opportunities, including the development of dual inhibitors and proteolysis-targeting chimeras (PROTACs), to fully exploit the therapeutic value of the MKK4/7-JNK axis.

Abstract: Acmella oleracea (L.) R. K. Jansen (Asteraceae), commonly known as the "toothache plant" or "jambu," is a significant medicinal plant that has been traditionally used in Brazil and other tropical and subtropical regions for relieving dental pain, as an anti-inflammatory agent, and as a culinary spice. Due to its versatile utility, this plant has been extensively studied in modern medicine and pharmacy for its diverse pharmacological properties, including anesthetic, analgesic, anti-inflammatory, antioxidant, and antimicrobial activities. Analytical research on the chemical compositions responsible for these activities has led to the identification of approximately 120 secondary metabolites. These findings provide scientific validation for its traditional uses and have spurred research into the development of ingredients for functional foods and cosmetics. This review incorporates the latest research findings, focusing on biological activities and compounds that have been practically isolated or can be isolated based on quantitative experimental data, to serve as a practical reference for industrial development. Furthermore, factors influencing the content of alkylamides and phenolic compounds, two major bioactive groups, are summarized to support material development. Ultimately, this review aims to provide a clearer understanding of the plant’s utility and contribute to the development of products that enhance human health.

Abstract: The human metapneumovirus (HMPV) Fusion (F) glycoprotein is a high-priority target for "fusion-locking" agents that stabilize its metastable prefusion state. While monomeric catechins like EGCG are known antivirals, the molecular basis for the superior activity of structurally complex dimeric catechins remains poorly understood. We employed an advanced biophysical workflow, integrating 100 ns all-atom Molecular Dynamics (MD), Free Energy Landscape (FEL) analysis, and MM/GBSA thermodynamic integration to decode the Structure-Dynamics Relationship (SDR) of 210 Camellia sinensis (Green tea) phytochemicals. The results reveal a "Galloylation-Driven Anchoring" mechanism: the galloyl moiety of prodelphinidin A2 3′-gallate provides critical electrostatic complementarity to the Asp325-Asp336 acidic ridge. FEL analysis quantitatively demonstrates that this anchoring traps the F protein in a deep, kinetically stabilized global minimum (ΔG = 9.357 kJ/mol), effectively raising the energy barrier for the fusogenic conformational shift. This study provides a rigorous thermodynamic proof-of-concept for the use of dimeric natural scaffolds as precision fusion-locking agents, offering a roadmap for experimental biophysical validation.

Abstract: Photodynamic therapy (PDT) offers a promising complementary strategy for the treatment of glioblastoma multiforme (GBM); however, achieving selective activation in tumor tissue and maintaining efficacy under hypoxic conditions remain significant limitations. In this study, we present the synthesis and functional evaluation of Gal-SiX, an enzymatically activatable Si-xanthene photosensitizer designed to address these challenges. Prepared through an improved 10-step synthetic route, Gal-SiX displays a clear turn-on fluorescence and absorbance response upon β-galactosidase activation and generates reactive oxygen species efficiently in aqueous media. Mechanistic studies revealed that Gal-SiX enables both Type I and Type II PDT pathways, an advantageous feature for GBM, where oxygen availability is restricted. In vitro assays conducted on U87MG glioblastoma cells and L929 healthy fibroblasts demonstrated meaningful selectivity, with IC50 values of 3.30 μM and 7.19 μM, respectively. Gal-SiX also showed minimal dark toxicity (>80 μM) and potent light-induced cytotoxicity, yielding a phototoxicity index of 24.8 in glioblastoma cells. Confocal imaging and MTT assays consistently demonstrated its activation and PDT efficacy. Overall, this work introduces the first activatable Si-xanthene–based PDT agent for glioblastoma and provides the first evidence that the Si-xanthene scaffold can support dual Type I/II phototoxicity. These results underscore Gal-SiX’s potential as a selective PDT platform for addressing the unique constraints of GBM biology.

Abstract: Green cosmetics are mainly based on plant-derived ingredients, using sustainable bio-technological tools for their preparation. The present research aimed to investigate the Usnea barbata extract in Jojoba oil (JO) enriched with 10% Vitamin E and 5% Pepper-mint oil (PEO), as a potential natural product for skin applications. Materials and Methods: The U. barbata extract (UBPJO) was obtained through cold maceration. Phytochemical screening was performed using Gas Chromatography/Mass Spectrometry (GC-MS), Folin Ciocalteu method, and Graphite-Furnace Atomic Absorption Spectro-photometry. The physicochemical properties were evaluated by Fourier Transform Infrared Spectroscopy and Atomic Force Microscopy. Then, rheological characteristics and oxidation stability (measuring the time required to reach the oxidation starting point, IP) of both oil samples (PJO and UBPJO), were investigated. Results: Total phenolic content in UBPJO was 2.5 times higher than in PJO (p < 0.05), while heavy metal levels (As and Pb) were slightly higher (p > 0.05). UBPJO has higher shear stress, viscosity, and spreadability than PJO, but without significant differences (p > 0.05). Finally, IP measurements indicated appreciable oxidative stability (UBPJO vs. PJO: 153.02 h vs 137.35 h, p > 0.05). Conclusions: The phytochemical composition and physicochemical properties support the inclusion of UBPJO in various skin-protective formulations.

Abstract: In 2025, the U.S. Food and Drug Administration (FDA) approved 44 new drugs, reflecting a slight decrease compared to previous years but maintaining the overall trends in pharmaceutical inno-vation. Biologics accounted for 25% of approvals, including eight monoclonal antibodies (mAbs), two antibody–drug conjugates (ADCs), and one fusion protein, with cancer remaining the primary therapeutic focus. TIDES, comprising three oligonucleotides and one peptide, continued to con-solidate their presence in the market, with the three oligonucleotides featuring N-acetylgalactosamine (GalNAc) for liver-targeted delivery. Small molecules dominate the re-mainder, with a high prevalence of N-aromatic moieties and fluorine atoms present in most of the molecules.. Peptide manufacturing and sustainability concerns, including PFAS usage, remain key challenges. Despite these advances, the high cost of innovative therapies limits access, particularly in low- and middle-income countries. This report provides a structural and chemical analysis of the newly approved drugs, highlighting trends in molecular design, therapeutic areas, and technolog-ical innovations shaping modern drug discovery.

Abstract: Neuroblastoma, a leading cause of pediatric cancer mortality, requires efficient and selective therapeutics. We synthesized and characterized a series of sulfonated 5-piperazine-containing 1,3-oxazole-4-carbonitrile derivatives via sulfonylation protocols and evaluated their in vitro cytotoxicity against human hepatocellular carcinoma (HepG2, Huh7), breast (MCF7, MDA-MB-231), cervical (HeLa), melanoma (M21), and two neuroblastoma (Kelly, SHSY5Y) cell lines, alongside non-malignant HEK293 cells. Three compounds (7a, 7b, and 8aa) demonstrated efficient and selective cytotoxicity toward MYCN-amplified (Kelly) and MYCN-non-amplified (SHSY5Y) neuroblastoma cells, with 7b being the most active (IC₅₀ = 1.9 µM in Kelly cells) and showing minimal toxicity in HEK293 (IC₅₀ > 10 µM). In Kelly cells, 7b matched doxorubicin while showing lower off-target toxicity and low-micromolar activity in solid tumors. The hit compounds were shown to be not readily biodegradable under OECD 301D test. In silico docking revealed high-affinity binding to the ATP-binding site of Aurora A kinase in the Aurora A/N-MYC complex (ΔG = –10.8 to –10.9 kcal/mol). Compound 7b exhibited broad cytotoxicity across all tested cancers (IC₅₀ = 1.5–4.0 µM). ADMET profiling of 7a, 7b, and 8aa indicated favorable pharmacokinetic and toxicity parameters compared with doxorubicin. These findings identify sulfonylated oxazole-4-carbonitriles as neuroblastoma therapeutics with potential use against proliferating malignancies.

Abstract: Marine triterpenoid saponins are structurally diverse metabolites with high pharmacological and nutraceutical potential, yet their characterization remains challenging due to extensive isomerism, aggregation phenomena, and the frequent co-extraction of lipids and other matrix components. In this work, we combine ATR–FTIR and high-resolution LC–MS to investigate the spectral and chromatographic behaviour of Cucumaria frondosa extracts and butanol-enriched fractions. FTIR spectra reveal a strong aliphatic signature, N–H-related features, and ester carbonyl bands consistent with the presence of co-extracted lipids and nitrogen-containing species such as ceramides or sphingolipids. LC–MS analysis of preparative fractions shows recurrent saponin-like ions— most prominently a feature at m/z ≈ 1347—reappearing across chromatographically distinct fractions, often accompanied by lipid-like ions in the 600–900 m/z range. These observations indicate that closely associated lipidic species can modulate the apparent chromatographic behaviour of saponin-containing fractions. Comparison with the Marine Animal Saponin Database (MASD v1.0) highlights both its value and its current MS1-centric limitations, including the lack of diagnostic MS/MS spectra and occasional inconsistencies between reported formulas and listed molecular weights. These findings underscore the need for integrated, multi-spectroscopic workflows and standardised spectral libraries to support confident annotation of marine saponins. Rather than proposing new structures, this study validates an analytical workflow that bridges early-stage MS screening with preparative fractionation and orthogonal spectroscopic assessment, offering a methodological reference to minimise misidentification and to guide future structural and biological investigations of marine triterpenoid saponins.

Abstract: Osteoarthritis (OA) is a prevalent chronic pain syndrome and a leading cause of disability worldwide, characterized by progressive deterioration of articular cartilage. This degradation leads to pain, swelling, inflammation, and eventual stiffness as the cartilage wears down, causing bone-on-bone friction. Current medical treatments primarily aim at pain relief; however, many interventions, especially invasive or surgical ones, carry risks of adverse outcomes. Consequently, intra-articular (IA) therapy, particularly hyaluronic acid (HA) injections, is widely adopted as a conservative treatment option. HA plays a crucial role in maintaining joint homeostasis by supporting proteoglycan synthesis and scaffolding, restoring optimal HA concentrations in synovial fluid, and providing chondroprotective and anti-inflammatory effects. In recent years, hydrogels composed of natural and synthetic materials have emerged as promising candidates for OA treatment. Our research focuses on the biosynthesis and characterization of novel hydrogel composites combining short peptide hydrogelators with aminated graphene oxide (a-GO) nanosheets functionalized with HA (a-GO-HA@Hgel). These a-GO-HA@Hgel nanocomposites are designed to facilitate the controlled release of HA into the extracellular matrix, aiming to promote cartilage regeneration and mitigate inflammation. The strategy is to exploit the oxygen-containing functional groups of GO nanosheets to enable covalent coupling or physical adsorption of HA molecules through various chemical approaches. The resulting a-GO-HA are incorporated within hydrogel matrices to achieve sustained and controlled HA release. We study the influence of a-GO-HA on the native hydrogel structure and its viscoelastic properties, which are critical for mimicking the mechanical environment of native cartilage tissue. Through this multidisciplinary approach combining advanced materials science and cellular biology, this work aims to develop innovative nanocomposite hydrogels capable of delivering HA in a controlled manner, enhancing cartilage repair and providing a potential therapeutic strategy for OA management.

Abstract: We herein demonstrate that the thiosemicarbazone (TSC) ligand N'-(di(pyridin-2-yl)methylene)-4-(thiazol-2-yl)piperazine-1-carbothiohydrazide (HL) can coordinate with Ga3+ to give the cationic complex of [Ga(L)2]NO3 featuring an the octahedral Ga(III) center. [Ga(L)2]NO3 may undergo metathesis with both Fe2+ and Fe3+ and result in the formation of respective Fe2+- and Fe3+ complex. Meanwhile, [Ga(L)2]NO3 is also susceptible to anion exchange with solidum hyaluronate (NaA) to produce the nanoformulation of [Ga(L)2]A with boosted aqueous solubility and cell targetability. [Ga(L)2]A demonstrated remarkable in vitro cytotoxicity against NCI-H82 and A549 (lung cancer), as well as KYSE-510 and Te-1 (esophageal cancer) cell lines, featuring half maximal inhibitory concentration (IC50) values in the range of 0.102 − 2.616 μmol L−1. This work highlights the potential of using non-toxic and biocompatible Ga3+ as the central ion to prepare TSC-based nanomedicines for combating cancer.