Search Results (179)

Background: Infections caused by the protozoan Trichomonas vaginalis affect millions of people worldwide and are responsible for one of the most common sexually transmitted diseases. Despite the efficacy of 5-nitroimidazoles like metronidazole, concerns regarding widespread resistance and the absence of viable alternatives for specific patient populations necessitate the development of structurally diverse pharmacological agents. In this study, we investigated the antiparasitic activity of 1,3-thiazolidin-4-one derivatives against T. vaginalis. Methods: Thiazolidines were synthesized via multicomponent reaction (MCR) using one-pot methodology and tested in vitro against the parasite and mammalian cell lines. Results: Seventy percent of the compounds showed more than 80% antiparasitic activity at 100 μM, with compounds 4a, 4b, and 4f exhibiting IC₅₀ ≤ 20 µM. None of the molecules exhibited cytotoxic against Vero CCL-81 and HeLa cells. Evaluation of the structure–activity relationship (SAR) indicates that the substituent at the nitrogen position of the heterocycle may be involved in the antiparasitic effect of these compounds. In silico studies also revealed that the three compounds possess adequate oral bioavailability and do not present mutagenic, tumorigenic or irritating risks. Finally, molecular docking predicted strong interactions of compounds 4a, 4b, and 4f with T. vaginalis enzymes lactate dehydrogenase and purine nucleoside phosphorylase; compound 4f also interacted with methionine Ƴ-lyase. Conclusions: These preliminary results suggest that 1,3-thiazolidin-4-ones are promising scaffolds for developing new trichomonacidal agents. Full article

Recently, the kinetic improvement of the nitrogenation reaction of lithium hydride (LiH) to form lithium imide (Li₂NH) by adding a scaffold was reported. The scaffold prevents agglomeration of Li₂NH and maintains the activity of LiH, achieving a reduction in reaction temperature and an increase in reaction rate. In this work, a Li–Si alloy, Li₂₂Si₅, was used as a starting material to form nano-sized LiH dispersed in a Li alloy matrix. Lithium nitride (Li₃N) is generated by the reaction between Li₂₂Si₅ and N₂ to form Li₇Si₃, and then Li₃N is converted to LiH with ammonia (NH₃) generation during heat treatment under H₂ flow conditions. Since Li₃N is formed at the nano-scale on the surface of alloy particles, LiH generated from the above nano-Li₃N is also nano-scale. The differential scanning calorimetry results indicate that direct nitrogenation of LiH in the alloy matrix occurred from around 280 °C, which is much lower than that of the LiH powder itself. Such a highly active state might be achieved due to the nano-crystalline LiH confined by the Li alloy as a self-transformed scaffold. From the above experimental results, the nano-confined LiH in the alloy matrix was recognized as a potential NH₃ synthesis technique based on the LiH-Li₂NH type chemical looping process. Full article

Background: 8-Quinolinol and its derivatives are drawing significant attention across various disciplines due to their remarkable versatility. These compounds are well-known for their exceptional chelating ability, forming stable metal complexes via their nitrogen and oxygen electron donor atoms. This main characteristic determines their broad utility. Biological activity can also be explained by the chelating capacity, which allows 8-quinolinol to bind to essential metal ions such as Fe, Zn, Cu, and others. This chelation disrupts metal-dependent biological processes in target cells or organisms, leading to a range of effects, including antimicrobial, anticancer, antifungal, and neuroprotective activities. On the other hand, the biological activity of pyrazole derivatives is attributed to their heterocyclic structure, which allows for interactions with biological targets that can lead to enzyme inhibition, receptor antagonism, radical scavenging, and other effects. Objective: This work aimed to synthesize and characterize novel diazene compounds derived from 8-quinolinol or 2-methyl-8-quinolinol and pyrazole amines, and to evaluate their antimicrobial and anticancer activities. Methods: The compounds have been synthesized by coupling diazonium salts obtained from the diazotization of heterocyclic amines with 8-quinolinol and its derivative, 2-methyl-8-quinolinol. The careful selection of reaction conditions enabled the synthesis of high-purity products. The compounds were characterized by 1D and 2D NMR, FT-IR spectroscopy, UV-Vis spectroscopy, and LC-HRMS analysis. The biological activity of the newly synthesized compounds was evaluated following the protocols of EU-OPENSCREEN, a European Research Infrastructure Consortium (ERIC) initiative dedicated to supporting early drug discovery. Results: By combining diazonium salts obtained from 3-methyl-1H-pyrazol-5-amine and ethyl 5-amino-3-methyl-1H-pyrazole-4-carboxylate with the aforementioned coupling agents, four novel 8-quinolinol derivatives were synthesized. The further hydrolysis of the ethoxy carbonyl functional group allowed its conversion to a carboxylic functional group, thus expanding the series of new compounds to six members. Several compounds from the series have proven to be biologically active against several human pathogenic microorganisms and the Hep-G2 cancer cell line. Conclusions: The combination of two well-known biologically active scaffolds through a classic diazo coupling reaction allowed the synthesis of novel biologically active compounds, which showed promising results as possible antifungal and anticancer agents. These results represent a foundation for future studies, which will include a broader biological screening and in vivo studies. Full article

Calcium phosphate cements (CPCs) and biomaterials, such as mesoporous bioactive glass (MBG), are critical for bone tissue engineering. This study aimed to 3D-print CPC scaffolds modified with MBG to enhance their osteogenic potential and regenerative ability. MBG powder was synthesized and characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD), and nitrogen adsorption–desorption techniques. A commercial CPC ink (hydroxyapatite/α-tricalcium phosphate) was mixed with 5% MBG (w/w; CPC/MBG), and, after rheological assessment, the mixture was used to obtain scaffolds via 3D printing. These scaffolds were then tested for chemical, morphological, and mechanical properties, as well as ion release analysis. Unmodified CPC 3D-printed scaffolds served as controls. Biological experiments, including cell viability, DNA content, cell adhesion/spreading, and osteogenic gene expression, were performed by seeding alveolar bone-derived mesenchymal stem cells onto the scaffolds. Statistics were performed using Student’s t-test and ANOVA with post hoc tests (α = 5%). MBG characterization showed a typical mesoporous structure with aligned microchannels and an amorphous structure. Both formulations released calcium and phosphate ions; however, CPC/MBG also released silicon. Cell viability, adhesion/spreading, and DNA content were significantly greater in CPC/MBG scaffolds compared to CPC (p < 0.05) after 3 and 7 days of culture. Furthermore, CPC/MBG supported increased expression of key osteogenic genes, including collagen (COL1A1), osteocalcin (OCN), and Runt-related transcription factor 2 (RUNX2), after 14 days (p < 0.05). The combination of CPC ink with MBG particles effectively enhances the biocompatibility and osteogenic potential of the scaffold, making it an innovative bioceramic ink formulation for 3D printing personalized scaffolds for bone regeneration. Full article

Compounds based on an isoquinoline scaffold (benzo[c]pyridine) display a broad spectrum of biological activities. In recent years, studies have focused mainly on their anticancer properties. Their antiproliferative effects are associated with diverse mechanisms that include targeting PI3K/Akt/mTOR signaling pathways and reactive oxygen species or inducing apoptosis and cell cycle arrest. Furthermore, isoquinolines may inhibit microtubule polymerization, topoisomerase, or tumor multidrug resistance. Recent studies have also shown that these compounds may act as effective antimicrobial, antifungal, antiviral, and antiprotozoal agents. Moreover, it has also been demonstrated that isoquinoline derivatives exhibit potent anti-Alzheimer effects, alleviating central nervous system functions. Additionally, they possess anti-inflammatory and antidiabetic properties. Due to the presence of donor nitrogen, the isoquinoline core constitutes an appropriate ligand that may be employed for the development of metal complexes with improved pharmacological properties. A number of chelates containing copper, iridium, or platinum were found to exhibit prominent biological activity, which places them in a leading position for the development of effective medications. This review summarizes the recent development of synthetic isoquinoline-based compounds with proven pharmacological properties in the period of 2020–2025. Also, other biomedical applications for synthetic isoquinoline derivatives are provided. Full article

This study looked at a fungal–cyanobacterial co-pellet system for cleaning up coffee waste and producing high-value polymers. Optimization focused on the pelletization process, waste removal efficiency, and biomass yield. Optimal conditions, including pH (6.5), glucose concentration (6 g/L), and shaking speed (130 rpm), achieved a maximum cyanobacterial immobilization efficiency of up to 97% on the fungal mycelium. Scanning electron microscopy (SEM) confirmed the formation of an integrated co-pellet structure, with fungal hyphae acting as a physical scaffold and extracellular polymeric substances (EPSs) enhancing cell–cell adhesion. The co-culture system exhibited superior performance compared to fungal (20.56 g/L) and algal (1.09 g/L) monocultures. It effectively removed major coffee effluent pollutants, achieving a significant reduction in total phenolic compounds (74.5%). Furthermore, the co-pellets displayed a remarkable final biomass yield (24.33 g/L) and high production of extracellular polymeric substances (EPSs) (5.28 g/L) and intracellular polymeric substances (IPSs) (3.84 g/L). The synergistic relationship was further confirmed by high nitrogen contents in the co-pellets (15.24%), which significantly surpassed that of the individual fungal biomass, suggesting interspecies nutrient transfer. Valuable glycerol-lipids were detected and identified in the fermentative broth of the co-culture confirming a highly efficient bioconversion process. Analyses revealed a targeted metabolic flow toward the accumulation of monoglycerides, notably monooleoylglycerol and monopalmitin, highlighting a powerful cooperative compatibility for producing high-value emulsifiers. Overall, these findings firmly establish the cyano-fungal co-pellet system as a robust and sustainable biorefinery approach for treating complex industrial wastewater while producing a high-quality, value-added biomass suitable for utilization as a biofertilizer or animal feed. Full article

Background/Objectives: Heterofunctional cationic polyester dendrimers derived from a 2-(bromomethyl)-2-(hydroxymethyl)propane-1,3-diol (BHP-diol) based AB₂C monomer were evaluated as efficient and biodegradable nonviral carriers for siRNA delivery. Methods: These dendrimers feature dual internal and external charge architectures, enabling precise control of charge distribution and siRNA interaction strength. Results: They achieved complete siRNA complexation at nitrogen-to-phosphate (N/P) ratios of 0.50–2.14 and provided up to 93% RNase protection, outperforming amino-functional scaffolds based on 2,2-bis(methylol)propionic acid (bis-MPA). In human (T98G) and murine (GL261) glioblastoma cells, the dendrimers exhibited minimal cytotoxicity while achieving 52–61% target protein knockdown, a two- to three-fold improvement over conventional polyester dendrimers, and approaching the silencing efficiency of the commercial Interferin^® reagent. Conclusions: The combination of high complexation efficiency, strong nuclease resistance, and excellent biocompatibility establishes these heterofunctional dendrimers as a new generation of precisely tunable, biodegradable vectors for therapeutic siRNA delivery. Full article

Caffeic acid phenethyl ester (CAPE), a polyphenol from propolis, is well recognized for its anti-inflammatory, antioxidant, antimicrobial, and osteogenic properties. This study aimed to develop macroporous bone scaffolds composed of a chitosan/agarose matrix reinforced with nanohydroxyapatite and enriched with stable CAPE derivatives to enhance their biomedical potential for applications in bone tissue engineering and regenerative medicine. A comprehensive evaluation of microstructural and biological properties of the produced scaffolds was conducted. The fabricated scaffolds exhibited high porosity (49–60%) with interconnected pores and compressive strength (1.2–1.8 MPa), closely resembling cancellous bone and indicating suitability for bone regeneration. They were biocompatible, promoted osteoblast adhesion, proliferation, and differentiation, and supported apatite deposition on their surfaces, demonstrating strong bioactivity and potential for implant osseointegration. Importantly, the scaffolds did not trigger excessive production of reactive oxygen or nitrogen species, suggesting a low risk of inflammatory responses. Additionally, CAPE-enriched scaffolds inhibited biofilm formation by Staphylococcus aureus and Staphylococcus epidermidis, reducing the risk of implant-associated infections. In summary, these CAPE-modified scaffolds integrate optimal microstructural and biological features, such as reducing oxidative stress and inhibiting biofilm formation, and thus offer a promising strategy for enhancing bone repair and regeneration in clinical applications. Full article

Aromatic ring systems appear ubiquitously in active pharmaceutical substances, such as FDA-approved histone deacetylase inhibitors. However, these rings reduce the water solubility of the molecules, which is a disadvantage during application. To address this problem, azaborine rings may be substituted for conventional aromatic ring systems. These are obtained by replacing two adjacent carbon atoms with boron and nitrogen. Incorporating B–N analogs in place of aromatic rings not only enhances structural diversity but also provides a strategy to navigate around patent-protected scaffolds. We synthesized azaborines, which are isosteric to naphthalene and indole, and utilized them as capping units for HDAC inhibitors. These molecules were attached to various aliphatic and aromatic linkers with different zinc-binding units, used in established active compounds. Nearly half of the twenty-four molecules tested exhibited inhibitory activity against at least one of the enzymes HDAC1, HDAC4, or HDAC8, with three compounds displaying IC₅₀ values in the nanomolar range. We have therefore demonstrated that azaborine building blocks can be successfully incorporated into HDACis, resulting in a highly active profile. Consequently, it should be feasible to develop active substances containing azaborine rings against other targets. Full article

Azomethine ylides (AMYs) have a nitrogen–carbon double bond and an electron lone pair on the nitrogen atom. They are essential 1,3-dipoles for [3+2] cycloadditions in the synthesis of pyrrolidine-containing heterocycles. Significant progress in 1,3-diplolar cycloadditions has been made in the construction of novel heterocyclic scaffolds, with efforts to broaden substrate scope, enhance stereoselectivity, and integrate green chemistry principles. This article summarizes double cycloadditions of AMYs derived from amino esters and amino acids for the synthesis of novel polyheterocycles. The design of double cycloadditions through the pot, atom, and step economic (PASE) method to increase the reaction efficiency is discussed. The examples presented in this paper may be applied to the synthesis of biologically active molecules. Full article

The reaction of 4′–bromo-fenamic acid, a bromo-derivative of fenamic acid (the scaffold of the fenamate non-steroidal anti-inflammatory drugs), with Co(II) in the absence or presence of various nitrogen-donor ligands yielded nine novel, neutral mononuclear Co(II) complexes. These complexes were characterized by physicochemical and spectroscopic techniques and single-crystal X-ray crystallography. The biological evaluation of the compounds focused on their antioxidant and antimicrobial efficacy, as well as their interaction with calf-thymus DNA, pBR322 plasmid DNA (in the absence or presence of diverse irradiations) and serum albumins. The complexes have shown significant antioxidant activity since they can scavenge 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radicals (up to 96.48 ± 0.07%) and reduce H₂O₂ (up to 96.93 ± 0.53%). Antimicrobial testing revealed that the complexes were more active than free 4′-bromo-fenamic acid with four of them classified as bactericidal agents against selected bacterial strains. The compounds can interact with calf-thymus DNA via intercalation, and the calculated DNA-binding constants are on the 10⁶ M⁻¹ order. The plasmid DNA-cleavage ability of the compounds is strongly enhanced under UVA irradiation (photocleavage > 90%). In addition, the compounds can bind tightly and reversibly to serum albumins with binding constants in the 10⁵ M⁻¹ range. Full article

We present the rational design of nanosized Pt nanocrystals immobilized on biomass-derived porous carbon matrices (Pt/BPC) through a convenient and eco-friendly strategy using wheat flour as a sustainable precursor. Interestingly, the three-dimensional BPC conductive network with optimized pore geometry enables enhanced metal–support interaction through d-orbital electron coupling, while the nitrogen-rich carbon scaffold provides abundant nucleation sites for the growth of ultrasmall Pt and effectively prevents them from aggregation. Accordingly, the resultant Pt/BPC catalyst demonstrates exceptional methanol oxidation performance with a large electrochemical surface area, a high mass activity of 1232.5 mA mg⁻¹, and excellent long-term stability, representing significant improvements over conventional carbon (e.g., carbon black, carbon nanotube, graphene, etc.)-supported Pt catalysts. Full article

In recent years, apatite-based materials have garnered significant interest, particularly for applications in tissue engineering. Apatite is most commonly employed as a coating for metallic implants, as a component in composite materials, and as scaffolds for bone and dental tissue regeneration. Among its various forms, hydroxyapatite (HAP) is the most widely used, owing to its natural occurrence in human and animal hard tissues. An emerging area of research involves the use of fluoride-substituted apatite, particularly fluorapatite (FAP), which can serve as a direct fluoride source at the implant site, potentially offering several biological and therapeutic advantages. However, substituting HAP with FAP may lead to unforeseen changes in material behavior due to the differing physicochemical properties of these two calcium phosphate phases. This study investigates the effects of replacing hydroxyapatite with fluorapatite in ceramic–polymer composite materials incorporating β-1,3-glucan as a bioactive polymeric binder. The β-1,3-glucan polysaccharide was selected for its proven biocompatibility, biodegradability, and ability to form stable hydrogels that promote cellular interactions. Nitrogen adsorption analysis revealed that FAP/glucan composites had a significantly lower specific surface area (0.5 m²/g) and total pore volume (0.002 cm³/g) compared to HAP/glucan composites (14.15 m²/g and 0.03 cm³/g, respectively), indicating enhanced ceramic–polymer interactions in fluoride-containing systems. Optical profilometry measurements showed statistically significant differences in profile parameters (e.g., Rp: 134 μm for HAP/glucan vs. 352 μm for FAP/glucan), although average roughness (Ra) remained similar (34.1 vs. 27.6 μm, respectively). Microscopic evaluation showed that FAP/glucan composites had smaller particle sizes (1 μm) than their HAP counterparts (2 μm), despite larger primary crystal sizes in FAP, as confirmed by TEM. XRD analysis indicated structural differences between the apatites, with FAP exhibiting a reduced unit cell volume (524.6 ų) compared to HAP (528.2 ų), due to substitution of hydroxyl groups with fluoride ions. Spectroscopic analyses (FTIR, Raman, ³¹P NMR) confirmed chemical shifts associated with fluorine incorporation and revealed distinct ceramic–polymer interfacial behaviors, including an upfield shift of PO₄³⁻ bands (964 cm⁻¹ in FAP vs. 961 cm⁻¹ in HAP) and OH vibration shifts (3537 cm⁻¹ in FAP vs. 3573 cm⁻¹ in HAP). The glucan polymer showed different hydrogen bonding patterns when combined with FAP versus HAP, as evidenced by shifts in polymer-specific bands at 888 cm⁻¹ and 1157 cm⁻¹, demonstrating that fluoride substitution significantly influences ceramic–polymer interactions in these bioactive composite systems. Full article

Quinazolin-4(3H)-ones are nitrogen heterocycles that have attracted considerable interest over many years due to their important biological and pharmacological properties. It has been shown that quinazolinone derivatives exhibit, e.g., analgesic, anti-inflammatory, antibacterial, anticonvulsant, antifungal, and antitumor activities. Some of these compounds have found applications in medicine; for instance, Zydelig (Idelalisib) has been approved for the treatment of several types of blood cancers. Furthermore, the quinazolinone skeleton is an important structural moiety present in many naturally occurring alkaloids, such as Febrifugine, a potent anti-malarial agent. To date, numerous synthetic methods have been developed for the synthesis of quinazolinone derivatives. Among them, multicomponent reactions (MCRs) have emerged as a powerful tool, allowing for the rapid and straightforward construction of the quinazolinone scaffold from readily available substrates. This review article presents a concise overview of selected strategies for synthesizing quinazolinone frameworks via one-pot MCRs. The reported methods are categorized into three main groups: metal-catalyzed reactions; isatoic-anhydride-based strategies, utilizing isatoic anhydride as a key starting material, and alternative approaches involving, among others, the utilization of N-(2-aminobenzoyl)benzotriazoles or aryldiazonium salts as efficient building materials. Full article

Benzothiazole derivatives have emerged as being highly significant in drug discovery due to their versatile biological activities and structural adaptability. Incorporating nitrogen and sulfur, this fused heterocyclic scaffold exhibits wide-ranging pharmacological properties, including anticancer, antimicrobial, anti-inflammatory, antidiabetic, neuroprotective, and diagnostic applications. A diverse set of clinically approved and investigational compounds, such as flutemetamol for Alzheimer’s diagnosis, riluzole for ALS, and quizartinib for AML, illustrates the scaffold’s therapeutic potential in varied applications. These agents act via mechanisms such as enzyme inhibition, receptor modulation, and amyloid imaging, demonstrating the scaffold’s high binding affinity and target specificity. Advances in synthetic strategies and our understanding of structure–activity relationships (SARs) continue to drive the development of novel benzothiazole-based therapeutics with improved potency, selectivity, and safety profiles. We also emphasize recent in vitro and in vivo studies, including drug candidates in clinical trials, to provide a comprehensive perspective on the therapeutic potential of benzothiazole-based compounds in modern drug discovery. This review brings together recent progress to help guide the development of new benzothiazole-based compounds for future therapeutic applications. Full article