Search Results (226)

A series of 1,2,3-triazole-linked-thiazolidine-2,4-dione hybrids (SDP1–SDP15) were designed, synthesized, and evaluated for their antidiabetic potential. All structures were characterized by FT-IR and NMR spectroscopy (¹H and ¹³C). All derivatives exhibited significant in vitro inhibition of α-glucosidase (IC₅₀: 24.17–46.41 µg/mL) and α-amylase (23.25–50.66 µg/mL), comparable to the standard drug acarbose (IC₅₀: 25.18 and 32.53 µg/mL) and superior to the reference drug pioglitazone (IC₅₀: 84.24 and 79.74 µg/mL) for α-glucosidase and α-amylase, respectively. Molecule SDP8 emerged as the most potent with an IC50 of 24.17 and 23.25 µg/mL for α-glucosidase and α-amylase, respectively. Further, SDP8 exhibited a higher docking score of −10.7 kcal/mol and −10.4 kcal/mol against α-glucosidase and α-amylase than pioglitazone (−8.1 kcal/mol and −7.7 kcal/mol, respectively), suggesting that interaction with these two enzymes may be the cause for its antidiabetic activity. Furthermore, DFT analysis revealed favorable electronic properties with a low HOMO-LUMO energy gap, whereas ADMET predictions revealed moderate drug-like characteristics with some limitations, such as poor solubility, relatively high lipophilicity, and partial noncompliance with drug-likeness regulations. Overall, these results highlight triazole-linked thiazolidinedione hybrids as promising candidates for further development in T2DM, with SDP8 serving as a preliminary lead requiring additional optimization and validation. Full article

Background/Objectives: Drug administration by microneedle patch (MNP) offers advantages over conventional dosage forms as a painless, self-administered skin patch for parenteral delivery. Dissolvable MNPs are typically manufactured by casting an aqueous formulation containing dissolved active pharmaceutical ingredient (API) and excipients into a mold and allowing it to dry. This process can be detrimental to APIs that are sensitive to dissolution and drying during the casting process. Methods: This study presents a MNP fabrication process in which drug particles are suspended in an organic solvent carrier without being dissolved in the solvent. Results: We started with drug particles either as pure API or formulated with excipients to stabilize them. We then screened nine organic solvents, ranging from high (methanol) to low (toluene) polarity, to identify those that suspend the drug particles without dissolution or damage to the API. To guide formulation of stabilized drug particles, we generated a companion database of 16 common stabilizing excipients and measured their solubility in our panel of organic solvents to identify excipient–solvent combinations that did not lead to excipient dissolution. We generated a second database of 14 water-soluble polymers to serve as the microneedle matrix material and determined their solubility in our panel of solvents to identify solvents that enabled polymer dissolution. Using these data, we designed casting solutions that suspended particles of API (and excipients) in an organic solvent that dissolved a matrix polymer. Casting and drying these solutions on molds produced MNPs for delivery of three model compounds: lyophilized tetanus toxoid (i.e., a vaccine), methotrexate (i.e., a small molecule drug), and insulin (i.e., a biologic). Conclusions: We conclude that this fabrication method, guided by the excipient and polymer solubility databases, offers a novel method to produce MNPs by suspension casting of drugs in organic solvents. Full article

The search for harmless alternative solutions to protect crops has become urgent and has recently attracted widespread attention from researchers around the world focusing on natural polyphenols, which represent a treasure chest of molecules with potent activities. Due to the low water solubility of polyphenols, microemulsions were selected as nanovectors. Curcumin and mangiferin solubility in different excipients was evaluated by HPLC. Microemulsion was developed using pseudo-ternary phase diagrams. Sizes and polydispersity of microemulsion globules were evaluated by dynamic light scattering. Activity against Fusarium verticillioides was evaluated by a microdilution method. Vitamin E acetate was selected as the oily phase, Transcutol P as cosurfactant and Tween 80 as surfactant. S_mix was composed of Transcutol P and Tween 80 in a 1:2 gravimetric ratio and combined with oil-phase vitamin E acetate at a weight ratio of 3:1. Microemulsions were loaded with 5 mg/mL of each polyphenol and recovery results were 99.5% and 99.3% for curcumin and mangiferin, respectively. Sizes of the lipid phase were 121.7 ± 29.2 nm and 172.6 ± 19.3 nm, respectively, for mangiferin and curcumin microemulsions. F. verticillioides was very susceptible to both microemulsions with a very high activity at a dose of 0.9 mg/mL (log-4 reduction), evidencing a possible use of these nanoformulations to protect crops from F. verticillioides. Full article

Organic redox-active molecules are promising catholyte materials for aqueous organic redox flow batteries (AORFBs), yet they often suffer from low solubility and poor cycling stability. Herein, we report a series of water-soluble phenothiazine derivatives functionalized with quaternary ammonium groups. The optimized compound, N,N,N-trimethyl-1-(10H-phenothiazin-10-yl) propan-2-aminium chloride (TMiPrPTCl), exhibits exceptional solubility (2.69 M in water) and a high redox potential (0.902 V vs. SHE). A comparative study of four derivatives reveals that side-chain length and branching critically modulate both solubility and degradation pathways: while three-carbon-linked analogs N,N,N-trimethyl-3-(10H-phenothiazin-10-yl)propan-1-aminium chloride (TMPrPTCl) degrade primarily via irreversible oxidation to sulfoxide, two-carbon-linked species (TMiPrPTCl) undergo additional side-chain cleavage, leading to rapid capacity fade. Although the quaternization strategy successfully achieves record solubility, the electrochemical stability remains a key challenge. Post-cycling analysis confirms the loss of redox activity and the formation of inert products. This work highlights the delicate balance between solubility enhancement and molecular stability, providing clear design guidelines for future phenothiazine-based catholytes. Full article

Propolis is a bee product with a complex chemical composition that exhibits remarkable antifungal activity against C. albicans and can inhibit resistant biofilms thanks to its content of compounds such as flavonoids and phenolic acids. Its efficacy varies depending on its geographic origin: European propolis inhibits the initial formation of biofilms, while Brazilian propolis is superior at inhibiting mature biofilms. This product also possesses fungicidal and fungistatic properties comparable in efficacy to conventional drugs, such as nystatin, fluconazole, and chlorhexidine. The use of nanotechnology, such as nanoparticles or nanorods, has overcome the low solubility of propolis compounds, improving their bioavailability and reducing cell adhesion and hyphal formation. Moreover, the integration of propolis into dental materials demonstrate its versatility for preventing recurrent infections. The study of isolated compounds such as pinocembrin, galangin, and chrysin has facilitated the identification of specific mechanisms of action, and the application of molecules such as guttiferone E in photodynamic therapies and the discovery of quorum-sensing inhibitors, such as kaempferol, using in silico models have opened new avenues for blocking yeast communication and virulence. These findings position propolis as a multifaceted and promising therapeutic alternative, although there is a need to optimize formulations to ensure clinical safety and biocompatibility. In this review, we analyze research published around the world over the last 15 years on the effects of propolis against C. albicans biofilms. Full article

Aqueous organic flow batteries are a promising technology for large-scale energy storage, owing to their safety, low cost, and tunable molecular properties. Battery performance is critically governed by the redox potential, solubility, and stability of organic active species, making molecular design a central research priority. Yet, many current systems still rely on inorganic metal-based materials, which face challenges such as high cost and sluggish kinetics. This review outlines a systematic molecular-engineering framework for designing novel redox species, offering strategies to tailor solubility, redox potential, and molecular size in both organic compounds. Recent advances in mechanistic insight, functionalization, and structure-dependent electrochemical performance are summarized. Computational chemistry and machine learning are highlighted for accelerating high-throughput screening and property prediction, speeding up molecular optimization. Small molecules (1–4 rings), including quinones (C=O), alloxazines, phenazines, and indigo derivatives, which undergo reversible redox reactions involving nitrogen and/or carbonyl groups, have been explored as anolytes and/or catholytes in aqueous redox flow batteries. Key challenges remain, including limited electrochemical stability windows, insufficient solubility, and poor molecular stability, leading to low energy density and cycling degradation. Improving anolyte performance by simultaneously lowering redox potential and enhancing solubility and stability is therefore crucial for advancing both organic and broader redox-active battery systems. Computational and machine learning approaches for identifying and refining electrolyte molecules are also addressed, enabling efficient screening and molecular modification toward high-performance flow batteries. Full article

Cancer poses a serious threat to human life and health, and the number of new cancer and death cases worldwide is substantial, of which breast cancer is the most common among women. p-QM-1h is an organic small molecule with excellent anti-cancer activity, but it has low solubility and requires a high dosage, and it is not a targeted anti-tumor drug. In this study, p-QM-1h was loaded into a nanostructured lipid carrier (NLC) using the thin-film dispersion method to construct p-QM-1h-NLC, and its surface was modified with cetuximab (CTX) to construct CTX-p-QM-1h-NLC, which was tested for activity in 4T1 cells and tumor-bearing mice. The construction of CTX-p-QM-1h-NLC used Miglyol 812N as a liquid lipid, which effectively improved the solubility and encapsulation efficiency of p-QM-1h. Nanoparticles were uniform, well dispersed, and had good stability, and the CTX modification of p-QM-1h-NLC exhibited high connection efficiency and ensured antibody integrity. CTX-p-QM-1h-NLC exhibited effective anti-tumor activity in both 4T1 cells and tumor-bearing mice. The construction of CTX-p-QM-1h-NLC effectively improved the solubility of p-QM-1h, enhanced its therapeutic efficacy and reduced its drug dosage. It also had a certain targeting ability, increasing drug aggregation in tumor tissues. Flow cytometry and Western blot results showed that CTX-p-QM-1h-NLC could effectively inhibit the expression of TrxR and increase the expression of Bax and caspase 3 in vivo, which was consistent with the increase in ROS levels and the induction of apoptosis in 4T1 cells. These results indicated that the construction of CTX-p-QM-1h-NLC is worthy of further investigation. Full article

Terpenoids represent a large class of bioactive natural compounds with promising pharmacological properties, including anti-inflammatory, antimicrobial, and anticancer activities. However, their clinical application is often limited by poor aqueous solubility, low membrane permeability, and suboptimal bioavailability. Phytosomal delivery systems have emerged as a promising strategy to enhance the pharmacokinetic performance of plant-derived compounds by forming molecular complexes between bioactive molecules and phospholipids. This review critically examines the structural principles, preparation methods, physicochemical characterization, and biological performance of terpenoid phytosomes. Particular attention is given to the molecular interactions between terpenoids and phospholipids that govern complex formation and vesicular assembly. The review also summarizes current analytical techniques used to confirm phytosome formation and discusses the influence of formulation parameters, including phospholipid composition and molar ratios, on stability and biological activity. In addition, emerging insights from molecular modeling and membrane interaction studies are considered to better understand the mechanisms underlying improved drug delivery. Finally, challenges related to safety assessment, manufacturing scalability, and clinical translation of phytosomal systems are discussed. Overall, terpenoid phytosomes represent a promising nanodelivery platform capable of improving the pharmacokinetic profile and therapeutic potential of terpenoid compounds. Full article

Mineral scale deposition remains a major flow-assurance constraint in oil and gas operations, especially in water-flooding and produced-water reinjection, where mixing between incompatible brines promotes super-saturation and precipitation of poorly soluble salts. This work introduces a novel extension of traditional methods used for modeling chemical inhibition and the predictive evaluation of oilfield scale-inhibitor molecules. A systematically optimized Two-Dimensional Quantitative Structure–Activity Relationship Model based on the k-Nearest Neighbors algorithm 2D-QSAR-KNN model was developed to quantitatively link molecular constitution of phosphonate inhibitors, brine chemistry, and operating factors with inhibition efficiency IE %. The optimized model achieved strong accuracy and generalization R²_train = 0.9182, R²_test = 0.9306, and R²_global = 0.9208 with low prediction errors RMSE_train = 4.7888%, RMSE_test = 4.5485%, and RMSE_global = 4.7421%. Median absolute errors remained minimal for the train set = 0.80%, and test set = 1.63%, and model stability was confirmed by high correlation with experimental IE % r = 0.94 and R²_train/R²_test ≈ 0.99, showing no sign of overfitting. Additionally, an inverse-2D-QSAR framework was applied to identify the optimal molecular descriptor profile expected to maximize inhibitory performance within normalized bounds, providing rational rules for next-generation inhibitor design. The findings highlight the practical value of QSAR-inspired AI modeling to accelerate molecule screening and dosage exploration prior to laboratory validation, supporting more cost-effective, interpretable, and environmentally aware sulfate-scale inhibition strategies under high-salinity reservoir conditions. Full article

Type 2 diabetes (T2D) features insulin resistance that promotes cerebrovascular injury, yet the immune signals linking metabolic stress to vascular dysfunction remain unclear. We tested the hypothesis that insulin resistance and soluble vascular cell adhesion molecule-1 (sVCAM1) act through complementary pathways in mast cells (MCs) to raise circulating histamine levels and impair cerebral vascular function. In a high-fat diet (HFD) plus low-dose streptozotocin (STZ) model, plasma histamine rose sharply after the onset of insulin resistance and remained elevated. Plasma sVCAM1 levels also increased after insulin resistance. In vitro, recombinant sVCAM1 upregulated histidine decarboxylase (HDC) in native MCs in a dose-dependent manner, indicating a shift toward histamine synthesis, but did not enhance degranulation. In contrast, pharmacological inhibition of Akt with MK2206 activated Glycogen Synthase Kinase 3 beta (GSK3β) and increased MC degranulation without affecting HDC expression. Diabetic endothelial cell monolayers exhibited a ~twofold reduction in transendothelial electrical resistance consistent with impaired blood–brain barrier (BBB) integrity. Diabetic cerebral arteries showed receptor remodeling that favored constriction with histamine H1 receptor (H1R) expression increasing in vascular smooth muscle, while endothelial H1R and histamine H2 receptor (H2R) decreased. Functionally, insulin treatment lowered HOMA2-IR in T2D mice but did not restore cerebral artery myogenic tone or improve stroke outcomes after distal middle cerebral artery occlusion (dMCAO). Neutralizing VCAM1 with a monoclonal antibody reduced circulating sVCAM1 and histamine levels, and, together with the GSK3β inhibitor Tideglusib, stabilized MCs, normalized cerebral artery tone, and reduced post-MCAO infarct size and edema. These findings identify two distinct yet complementary mast cell pathways in T2D, highlight an immune-vascular interface that drives cerebrovascular dysfunction, and propose sVCAM1 blockade plus GSK3β inhibition as rational strategies to protect cerebral vascular function in the diabetic brain. Full article

Background/Objectives: Chronic inflammation underlies many immune-mediated conditions, yet current anti-inflammatory therapies are often limited by incomplete efficacy or safety concerns. Small molecules inspired by soluble epoxide hydrolase (sEH) inhibitors represent a promising scaffold for early-stage exploration. This study describes the design, synthesis, and preliminary biological evaluation of three series of arylurea derivatives (ACBUs) to establish structure–activity relationships and guide chemical optimization. Methods: The compounds were assessed for effects on keratinocyte proliferation, human sEH activity, and the expression of selected inflammatory markers using IL-17A/TNF-α-stimulated HaCaT cells, a relevant in vitro model for preliminary anti-inflammatory profiling. Results: A total of 23 novel ACBU derivatives were synthesized and evaluated. Most compounds showed low antiproliferative activity, allowing selection based on cytotoxicity and solubility. Compounds 4b, 10b, and 16b consistently displayed the most favorable profiles in these preliminary assays. Docking studies provided structural rationales supporting the observed trends and guided further optimization within the series. Conclusions: Compound 4b emerged as the most active candidate in preliminary screening, serving as a reference for ongoing SAR studies. These results highlight the potential of the arylurea scaffold for further chemical optimization and demonstrate the value of early-stage biological profiling in guiding our further studies. Full article

Leishmaniasis remains an important neglected tropical disease, and current treatments are limited by toxicity, resistance, and low bioavailability. In this study, novel guanidine derivatives were evaluated through an integrated approach, combining in silico physicochemical profiling with in vitro biological assays using Leishmania (Viannia) braziliensis, the etiological agent of American Tegumentary Leishmaniasis (ATL). Most compounds exhibited favorable drug-like properties, though variations in lipophilicity and solubility influenced biological performance. Among the tested molecules, FURL-G5 emerged as the most promising candidate, showing potent activity against promastigote forms and low cytotoxicity in murine macrophages, resulting in high selectivity indices (SI > 10), comparable to those of LQOF-G1, a compound with previously established leishmanicidal effects. These compounds were also tested on intracellular amastigotes, drastically reducing the infection rate of macrophages. The integration of an in silico approach and biological validation enabled rational compound prioritization and supports the early-stage development of these scaffolds. Overall, this study reinforces the potential of guanidine-based compounds as leads for innovative ATL drug discovery and demonstrates the value of multidisciplinary strategies for identifying selective and safe therapeutic candidates. Full article

Microalgae display remarkable resilience to harsh environments, partly through the biosynthesis of diverse secondary metabolites. Cyanobacteria and red algae are well known to produce mycosporine-like amino acids (MAAs)—low-molecular-weight, water-soluble UV-absorbing compounds with anti-inflammatory, anticancer, and antimicrobial activities. By contrast, green microalgae typically lack detectable MAAs under standard conditions, and their responses under abiotic stress remain poorly characterized. Here, we investigated the freshwater green microalga Jaagichlorella luteoviridis grown under three stressors (salinity, heat, and UV) and assessed MAA induction. High-performance liquid chromatography (HPLC) revealed that stressed cultures accumulated multiple MAAs, whereas untreated controls showed no such accumulation. All stress treatments (UV, salinity, and heat) produced a substantial increase in peak intensity at 323–350 nm, whereas the control samples showed significantly lower absorption in this region. We also optimized an MAA extraction protocol suitable for “green” downstream applications in the pharmaceutical, nutraceutical, and cosmeceutical sectors and formulated an emulsion showing preliminary positive results and exhibiting an increased SPF index from 3.60 (control) to 3.78 when 0.2% MAA extract was added. Transcriptomic profiling against a reference genome revealed stress-specific differential gene expression and overexpression of specific genes of the MAA pathway, like ArioC and AroM/Aro1 SAM methyltransferases, thus identifying candidate targets for engineering enhanced MAA production. Given market demand for environmentally friendly and safe bioactives, microalgae represent a promising source of these valuable molecules. Full article

Supramolecular nanoparticles offer an efficient strategy to enhance the solubility, stability, and bioavailability of poorly water-soluble therapeutic molecules. In this study, water-dispersible SNPs were successfully prepared from dicarboxyl-bis-pillar[5]arene (H) and cetyltrimethylammonium bromide (CTAB) using a microemulsion method. Dynamic light scattering revealed that the resulting CTAB/H nanoparticles possessed a size distribution centered around 40 nm, a positive surface charge (+15 mV), and exhibited high colloidal stability over three months. ¹H NMR, 2D TOCSY, 2D NOESY, diffusion ordered NMR spectroscopy, and UV-Vis investigations confirmed the inclusion of the CTAB alkyl chain within the pillar[5]arene cavity, supporting the formation of stable supramolecular assemblies capable of efficiently encapsulating the poorly water-soluble flavonol quercetin (Q). The CTAB/H system displayed low cytotoxicity (up to 50 µg/mL) and pronounced antioxidant activity, as evidenced by DPPH, ABTS, and FRAP assays. Quercetin-loaded nanoparticles (CTAB/H/Q) enhanced cellular uptake and exhibited a marked cytoprotective effect against H₂O₂-induced oxidative stress in NIH-3T3 fibroblasts. Full article

Inflammation is the body’s natural immune response to invasion by foreign pathogens and is closely linked to many diseases. Chronic inflammation, if not properly controlled, can pose serious health risks and even threaten life. Currently, the main anti-inflammatory drugs are classified into steroidal and non-steroidal anti-inflammatory drugs, but both have significant side effects that limit their clinical applications. α-Hederin, a pentacyclic triterpenoid saponin, is derived from various plants, including Pulsatilla chinensis, Hedera helix, and Nigella sativa. It has been reported that α-hederin can be used to treat both acute and chronic inflammatory diseases. However, it has poor water solubility and low bioavailability. This study shows that α-hederin can directly self-assemble into a hydrogel through hydrogen bonds and van der Waals forces, called He-Gel. The mechanical properties of He-Gel were further characterized using rheological and microrheological methods. Its self-assembly mechanism was comprehensively elucidated through a combination of spectroscopic analyses and computational chemistry. Furthermore, in vitro experiments showed that He-Gel exhibits lower cytotoxicity and more excellent anti-inflammatory activity compared to free α-hederin. In conclusion, this research provides a solution for the further development of α-hederin. Unlike conventional approaches that rely on polymers as drug carriers, this preparation method is both green and economical. More importantly, it highlights that direct self-assembly of natural small molecules represents a promising strategy for anti-inflammatory therapy. Full article