Search Results (1,064)

Staurosporine (STS) was discovered in 1977 by Omura and colleagues during a chemical screening for microbial alkaloids. It was the first indolocarbazole compound isolated from a soil-dwelling bacterium, Streptomyces staurosporeus. STS was also found to have antifungal activity, but its potent protein kinase (PK) inhibitory properties, perhaps the most extensively characterized biochemical feature of STS, were only revealed nearly a decade after its discovery. Thereafter, STS has been studied mainly for its anticancer potential with foreseen applications ranging from biomedical (e.g., antiparasitic) to agricultural (e.g., insecticidal). Interestingly, the recent discovery that STS induces apoptosis in the filamentous fungus Neurospora crassa renewed interest in this molecule as a scaffold for antifungal drug development. Studies in fungi and mammalian cell lines suggest that, in addition to PK inhibition, other modes of action are possible for STS. These may involve the targeting of membrane lipid domains and/or alterations of membrane biophysical properties. Here, the studies on the action of STS and its natural and synthetic derivatives against diverse fungal species, since its discovery to the present day, are critically reviewed and discussed with the aim of highlighting their advantages, limitations to be overcome, conceivable mechanisms of action, and potential as antifungal chemotherapeutic agents. Full article

Hydrogels are hydrophilic, soft polymer networks with high water content and mechanical properties that are tunable; they are also biocompatible. Therefore, as biomaterials, they are of interest to modern medicine. In this review, the main applications of hydrogels in essential clinical applications are discussed. Chemical, physical, or hybrid crosslinking of either synthetic or natural polymers allow for the precise control of hydrogels’ physicochemical properties and their specific characteristics for certain applications, such as stimuli-responsiveness, drug retention and release, and biodegradability. Hydrogels are employed in gynecology to regenerate the endometrium, treat infections, and prevent pregnancy. They show promise in cardiology in myocardial infarction therapy through injectable scaffolds, patches in the heart, and medication delivery. In rheumatoid arthritis, hydrogels act as drug delivery systems, lubricants, scaffolds, and immunomodulators, ensuring effective local treatment. They are being developed, among other applications, as antimicrobial coatings for stents and radiotherapy barriers for urology. Ophthalmology benefits from the use of hydrogels in contact lenses, corneal bandages, and vitreous implants. They are used as materials for chemoembolization, tumor models, and drug delivery devices in cancer therapy, with wafers of Gliadel presently used in clinics. Applications in abdominal surgery include hydrogel-coated meshes for hernia repair or Janus-type hydrogels to prevent adhesions and aid tissue repair. Results from clinical and preclinical studies illustrate hydrogels’ diversity, though problems remain with mechanical stability, long-term safety, and mass production. Hydrogels are, in general, next-generation biomaterials for regenerative medicine, individualized treatment, and new treatment protocols. Full article

Cytisine, a naturally occurring alkaloid and partial agonist of nicotinic acetylcholine receptors (nAChRs), has long been used as a smoking cessation aid and serves as the pharmacophore for varenicline. Recent research has expanded its therapeutic scope to neurodegenerative and neurological disorders, motivating the development of new cytisine derivatives. Among these, N-propargylcytisine combines the biological activity of the parent compound with the synthetic versatility of the terminal alkyne group. Herein, we report the synthesis and characterization of N-propargylcytisine, and its symmetrical dimer linked through 1,3-diyne moiety obtained via a copper-mediated Glaser–Hay oxidative coupling. The products were analyzed by NMR, FT-IR, and mass spectrometry, confirming the introduction of the propargyl moiety and the formation of the diyne bridge. Solvatochromic study of both compounds were performed using UV-VIS absorption spectroscopy in solvents of varying polarity, including protic solvents capable of hydrogen bonding. The 1,3-diyne motif, commonly found in bioactive natural products, endows the resulting dimer with potential for further derivatization and biological evaluation. This study demonstrates the utility of the Glaser–Hay reaction in the functionalization of alkaloid scaffolds and highlights the prospects of N-propargylcytisine derivatives in drug discovery targeting the central nervous system. Full article

The global transition to a circular bioeconomy is accelerating the demand for sustainable, high-performance materials. Filamentous fungi represent a promising solution, as they function as living foundries that transform low-value biomass into advanced, self-assembling materials. While mycelium-based composites have proven potential, progress has been predominantly driven by empirical screening of fungal species and substrates. To unlock their full potential, a paradigm shift from empirical screening to rational design is required. This review introduces a conceptual framework centered on the biochemical programming of the fungal cell wall. Viewed through a materials science lens, the cell wall is a dynamic, hierarchical nanocomposite whose properties can be deliberately tuned. We analyze the contributions of its principal components—the chitin–glucan structural scaffold, the glycoprotein functional matrix, and surface-active hydrophobins—to the bulk characteristics of mycelium-derived materials. We then identify biochemical levers for controlling these properties. External factors such as substrate composition and environmental cues (e.g., pH) modulate cell wall architecture through conserved signaling pathways. Complementing these, an internal synthetic biology toolkit enables direct genetic and chemical intervention. Strategies include targeted engineering of biosynthetic and regulatory genes (e.g., CHS, AGS, GCN5), chemical genetics to dynamically adjust synthesis during growth, and modification of surface chemistry for specialized applications like tissue engineering. By integrating fungal cell wall biochemistry, materials science, and synthetic biology, this framework moves the field from incidental discovery toward the intentional creation of smart, functional, and sustainable mycelium-based materials—aligning material innovation with the imperatives of the circular bioeconomy. Full article

Background: Corneal endothelial dysfunction continues to be a primary indication for corneal transplantation globally. Due to ongoing constraints in donor tissue availability and graft durability, artificial graft technologies are increasingly recognized as viable alternatives, particularly for eyes unsuitable for conventional allogeneic transplantation. Aim: This article examines the contemporary state of artificial corneal endothelial grafts, emphasizing technological advancements, incorporation into surgical procedures, and their developing function in meeting the unfulfilled requirements of endothelial keratoplasty. Methods: A comprehensive synthesis of recent preclinical and clinical literature was performed, concentrating on scaffold-based constructs, cell-seeded and acellular methodologies, biomaterial characteristics, and innovative surgical delivery techniques. The review highlights translational pathways and contrasts the initial outcomes of artificial and donor-derived endothelial grafts. Results: Advancements in regenerative biomaterials and cell culture systems have resulted in the development of functional endothelial substitutes. Engineered grafts, comprising decellularized stromal carriers, synthetic polymer matrices, and human cell-laden constructs, have demonstrated promising biocompatibility and functional results in preliminary trials. The integration of these constructs into methods akin to Descemet membrane endothelial keratoplasty (DMEK) has improved clinical viability, diminished immunologic risk, and shown potential for visual recovery. Conclusions: Artificial endothelial grafts signify a revolutionary advancement in corneal surgery, addressing donor shortages and expanding the applications of endothelial keratoplasty. Although additional clinical validation and regulatory processes are required, existing evidence indicates that these technologies may soon transform treatment protocols for corneal endothelial disease. Full article

Neural tissue injuries, including spinal cord damage and neurodegenerative diseases, pose a major clinical challenge due to the central nervous system’s limited regenerative capacity. Current treatments focus on stabilization and symptom management rather than functional restoration. Tissue engineering offers new therapeutic perspectives, particularly through the combination of electrospun nanofibrous scaffolds and mesenchymal stem cells (MSCs). Electrospun fibers mimic the neural extracellular matrix, providing topographical and mechanical cues that enhance MSC adhesion, viability, and neural differentiation. MSCs are multipotent stem cells with robust paracrine and immunomodulatory activity, capable of supporting regeneration and, under proper stimuli, acquiring neural-like phenotypes. This systematic review, following the PRISMA 2020 method, analyzes 77 selected articles from the last ten years to assess the potential of electrospun biopolymer scaffolds for MSC-mediated neural repair. We critically examine the scaffold’s composition (synthetic and natural polymers), fiber architecture (alignment and diameter), structural and mechanical properties (porosity and stiffness), and biofunctionalization strategies. The influence of MSC tissue sources (bone marrow, adipose, and dental pulp) on neural differentiation outcomes is also discussed. The results of a literature search show both in vitro and in vivo enhanced neural marker expression, neurite extension, and functional recovery when MSCs are seeded onto optimized electrospun scaffolds. Therefore, integrating stem cell therapy with advanced biomaterials offers a promising route to bridge the gap between neural injury and functional regeneration. Full article

Colorectal cancer (CRC) remains a major contributor to global cancer-related mortality, with rising incidence observed in several regions, including Saudi Arabia. This review compiles and critically analyzes recent preclinical research from Saudi-based institutions that investigates the anti-CRC potential of natural and synthetic compounds. Numerous natural products such as Nigella sativa, Moringa oleifera, Curcuma longa, and marine-derived metabolites have demonstrated cytotoxic effects through pathways involving apoptosis induction, reactive oxygen species (ROS) generation, and inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and cyclooxygenase-2 (COX-2). In parallel, synthetic and semi-synthetic agents, including C4–G4 (semi-synthetic hybrids designed from flavonoids and benzoxazole scaffolds that act as dual epidermal growth factor receptor (EGFR)/COX-2 inhibitors)), oxazole derivatives, and camptothecin-based nanocarriers, exhibit promising anti-tumor activity via molecular targeting of cyclin-dependent kinase 8 (CDK8), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), and β-catenin pathways. Selected in vivo studies primarily utilizing xenograft and chemically induced rodent models have shown reductions in tumor volume and modulation of apoptotic and inflammatory biomarkers. Additionally, green-synthesized metallic nanoparticles (NPs) and polyethylene glycol (PEG)-modified carriers have been investigated to improve bioavailability and tumor targeting of lead compounds. While these findings are encouraging, the majority remain in preclinical phases. Limitations such as poor solubility, lack of pharmacokinetic data, and absence of clinical trials impede translational progress. This review highlights the need for standardized evaluation protocols, mechanistic validation, and region-specific clinical studies to assess efficacy and safety. Given Saudi Arabia’s rich biodiversity and growing research capacity under national strategies like Vision 2030, the country is well-positioned to contribute meaningfully to CRC drug discovery. By integrating bioactive natural products, rationally designed synthetics, and advanced delivery platforms, a pipeline of innovative CRC therapeutics tailored to local and global contexts may be realized. Full article

Chrysin (5,7-dihydroxyflavone) is a flavonoid widely distributed in propolis, honey, and various plant sources. It exhibits a wide range of pharmacological activities, including anti-inflammatory, antioxidant, anticancer, antimicrobial, and anti-diabetic effects. However, its clinical translation is hampered by poor aqueous solubility, low bioavailability, and rapid metabolic clearance. To address these limitations and expand the chemical space of this natural scaffold, extensive synthetic efforts have focused on generating structurally diverse chrysin derivatives that possess improved drug-like properties. This review systematically categorizes synthetic methodologies—such as etherification, esterification, transition-metal-mediated couplings, sigmatropic rearrangements, and electrophilic substitutions—and integrates them with corresponding biological outcomes. Particular emphasis is placed on recent (2020–present) advances that directly link structural modifications with pharmacological enhancements, thereby offering comparative structure–activity relationship (SAR) insights. In addition, transition-metal-catalyzed C–C bond-forming reactions are highlighted in a dedicated section, underscoring their growing role in accessing bioactive chrysin analogs previously unattainable by conventional chemistry. Unlike prior reviews that mainly summarized biological activities or broadly covered flavonoid scaffolds, this article bridges synthetic diversification with pharmacological evaluation. It provides both critical synthesis and mechanistic interpretation. Overall, this work consolidates current knowledge and suggests future directions that integrate synthetic innovation with pharmacological validation and address pharmacokinetic challenges in chrysin derivatives. Full article

Background/Objectives: Targeted cancer therapies increasingly rely on modulating specific cell death pathways and kinase signaling. Due to their structural versatility and potential to induce mechanistically distinct cytotoxic responses, benzoxazine–purine hybrids represent a promising scaffold for anticancer drug development. The objective of this study was to design and evaluate novel benzoxazine–purine derivatives for their antiproliferative activity and elucidate their underlying mechanisms of action. Methods: A series of benzoxazine–purine compounds was synthesized via a modular and efficient approach. The synthetic route involved a one-pot cyclization of substituted 2-aminophenols with epichlorohydrin, followed by tosylation and subsequent Mitsunobu coupling with halogenated purines. Their antiproliferative activity was assessed in MCF-7 (breast) and HCT-116 (colon) cancer cell lines using MTT assays. Selected compounds were evaluated further for kinase inhibition, effects on the cell cycle, membrane integrity (Annexin V/PI staining), ultrastructural changes (SEM), and caspase activation (Western blot). In silico ADMET profiling was also performed. Results: Compounds 9 and 12 exhibited the most potent antiproliferative activity, with low micromolar IC₅₀ values. Compound 12 showed dual HER2/JNK1 kinase inhibition and induced caspase-8-dependent pyroptosis-like cell death, characterized by membrane rupture and inflammatory features. In contrast, compound 8 lacked kinase inhibition and promoted S-phase arrest with apoptotic-like morphology. Both compounds demonstrated favorable physicochemical and ADMET profiles, including high intestinal absorption and an absence of mutagenicity. Conclusions: The rational design of benzoxazine–purine hybrids resulted in the discovery of compounds with distinct mechanisms of action. Compound 12 induces inflammatory cell death by modulating kinases, while compound 9 acts through a kinase-independent apoptotic pathway. These results underscore the therapeutic potential of scaffold-based diversification for developing targeted anticancer agents. Full article

The growing threat of Antimicrobial Resistance (AMR) demands innovative drug discovery, yet conventional 2D cell cultures fail to accurately mimic in vivo conditions, leading to high failure rates in preclinical studies. This review addresses the critical need for more physiologically relevant platforms by exploring recent advancements in bioengineered 3D tissue models for studying bacterial pathogenesis and antimicrobial drug discovery. We conducted a systematic search of peer-reviewed articles from 2015 to 2025 across PubMed, Scopus, and Web of Science, focusing on studies that used 3D models to investigate host–pathogen interactions or antimicrobial screening. Data on model types, biomaterials, fabrication techniques, and key findings were systematically charted to provide a comprehensive overview. Our findings reveal that a diverse range of biomaterials, including biopolymers and synthetic polymers, combined with advanced techniques like 3D bioprinting, are effectively used to create sophisticated tissue scaffolds. While these 3D models demonstrate clear superiority in mimicking biofilm properties and complex host–pathogen dynamics, our analysis identified a significant research gap: very few studies directly integrate these advanced bioengineered 3D models for high-throughput antimicrobial drug discovery. In conclusion, this review highlights the urgent need to bridge this disparity through increased research, standardization, and scalability in this critical interdisciplinary field, with the ultimate goal of accelerating the development of new therapeutics to combat AMR. Full article

Hernia repair is among the most frequent procedures in general surgery, traditionally performed with synthetic meshes such as polypropylene. While effective in reducing recurrence, these materials are biologically inert and often trigger chronic inflammation, fibrosis, pain, and impaired abdominal wall function, with a significant impact on long-term quality of life. A comprehensive literature search was conducted in PubMed, Web of Science, and Scopus databases, and relevant preclinical, clinical, and review articles were synthesized within a narrative review framework. Recent advances in tissue engineering propose a shift from passive reinforcement to regenerative strategies based on biomimetic scaffolds, nanomaterials, and nanocomposites that replicate the extracellular matrix, enhance cell integration, and provide controlled drug delivery. Nanotechnology enables localized release of anti-inflammatory, antimicrobial, and pro-angiogenic agents, while electrospun nanofibers and composite scaffolds improve strength and elasticity. In parallel, 3D printing allows for patient-specific implants with tailored architecture and regenerative potential. Although preclinical studies show encouraging results, clinical translation remains limited by cost, regulatory constraints, and long-term safety uncertainties. Overall, these innovations highlight a transition toward personalized and regenerative hernia repair, aiming to improve durability, function, and patient quality of life. Full article

Background: Spinal deformity correction surgery, particularly in scoliosis, often necessitates long fusion constructs and complex osteotomies that create significant structural bone defects. These defects threaten the integrity of spinal fusion, potentially compromising surgical outcomes. Bone grafting remains the cornerstone of addressing these defects, traditionally relying on autologous bone. However, limitations such as donor site morbidity and insufficient graft volume have made urgent the development and adoption of biologic substitutes and synthetic alternatives. Additionally, innovations in three-dimensional (3D) printing offer emerging solutions for graft customization and improved osseointegration. Objective: This scoping review maps the evidence of the effectiveness of the use of biologic and synthetic bone grafts in scoliosis surgery. It focusses on the role of novel technologies, particularly osteobiologics in combination with 3D-printed scaffolds, in enhancing graft performance and surgical outcomes. Methods: A comprehensive literature search was conducted using PubMed, Scopus, and the Cochrane Library to identify studies published within the last 15 years. Inclusion criteria focused on clinical and preclinical research involving biologic grafts (e.g., allografts, demineralized bone matrix-DBM, bone morphogenetic proteins-BMPs), synthetic substitutes (e.g., ceramics, polymers), and 3D-printed grafts in the context of scoliosis surgery. Data were extracted on graft type, clinical application, outcome measures, and complications. The review followed PRISMA-ScR guidelines and employed the Arksey and O’Malley methodological framework. Results: The included studies revealed diverse grafting strategies across pediatric and adult populations, with varying degrees of fusion success, incorporation rates, and complication profiles. It also included some anime studies. Emerging 3D technologies demonstrated promising preliminary results but require further validation. Conclusions: Osteobiologic and synthetic bone grafts, including those enhanced with 3D technologies, represent a growing area of interest in scoliosis surgery. Despite promising outcomes, more high-quality comparative clinical studies are needed to guide clinical decision-making and standardize practice. Full article

Hypoxia and activation of the pentose phosphate pathway (PPP), as well as overexpression of glucose-6-phosphate dehydrogenase (G6PD), are hallmark features of glioblastomas (GBM), contributing significantly to tumor progression metabolic adaptation and drug resistance. This study aimed to evaluate the cytotoxic effects of nine synthetic compounds incorporating annulated benzimidazole and nitrothiazole scaffolds in two glioblastoma cell lines (A172 and U87-MG) under both normoxic and hypoxic conditions. Three compounds (BZM-7, BZM-9, and CNZ-3) demonstrated potent anticancer activity, with CNZ-3 exhibiting the highest efficacy, particularly in hypoxia. The study further investigated the effects of these compounds on the expression of the G6PD gene, as well as post-translational regulatory genes SIRT2 and KAT9, and the angiogenesis-related VEGF gene. Transcriptional analyses showed that the nitrothiazole-derived compound CNZ-3 significantly downregulated G6PD, SIRT2, KAT9 and VEGF expression under hypoxic conditions, suggesting selective interference with hypoxia-adaptative pathways. In contrast, BZM-7 and BZM-9 showed distinct expression patterns, indicating diverse mechanisms of action despite structural similarity. In addition, BZM-7, BZM-9, and CNZ-3 were identified as potent inhibitors of recombinant G6PD, demonstrating both enzymatic inhibition and structural alterations, suggesting that G6PD could be a relevant therapeutic target for these compounds. Furthermore, molecular docking analysis revealed favorable binding interactions between the compounds and key amino acids of the G6PD, reinforcing their potential as a direct enzyme inhibitors. These findings highlight the pivotal role of G6PD in gliomas under hypoxic conditions and support its inhibition as a promising therapeutic strategy. Full article

Modification of synthetic oligonucleotides and DNA is widely used in many applications in the life sciences. However, in most cases, modified DNA cannot be restored to its native state. Here, we report the preparation of a thymidine-inosine dimer building block (TID) for oligonucleotide synthesis. The TID modification supports the functionalization of synthetic oligonucleotides, which can later be removed to restore the DNA strand to its native state. The TID unit allows for a wide spectrum of postsynthetic modifications of oligonucleotides through click chemistry, including conjugation with fluorescent tags and small molecules, preparation of branched oligonucleotide scaffolds, and anchoring to a solid support. Due to the modification of the thymine base, the TID unit reduces the stability of the DNA duplex. We found that the negative effect of internal TID modification on duplex stability does not exceed the same for a single base mismatch. As long as the TID modification is present in the DNA strand, it disrupts its natural functionality. The “caging” effect of TID in the template strand with respect to DNA polymerase was demonstrated in primer extension experiments. Traceless removal of the temporary functional group occurs through oxidative cleavage of the inosine subunit, resulting in the formation of a native DNA strand with the thymine base left at the cleavage site. An anthracene-modified dodecamer oligonucleotide and a branched oligonucleotide scaffold were used to study the cleavage of the reporter group or the oligonucleotide side strand, respectively. It was shown that aqueous tetramethylguanidine efficiently cleaves the oxidized inosine subunit of TID at 37 °C, forming the native DNA strand. Full article

Quinazoline is a privileged heterocyclic scaffold commonly found in numerous pharmaceuticals and bioactive natural products, known for its diverse biological activities. The pursuit of efficient and versatile synthetic methods to produce quinazoline derivatives remains a central focus for organic and medicinal chemists, owing to the therapeutic potential of these compounds. This paper reviews the innovative use of 2-azidobenzaldehyde-enabled annulation strategies for the synthesis of quinazoline derivatives, including quinazolin-4(3H)-one, 2,3-dihydroquinazolin-4(1H)-one, 3,4-dihydroquinazoline, 3,4-dihydroquinazoline-2(1H)-thione, and 1,2,3,4-tetrahydroquinazoline. Emphasizing both the mechanistic insights and practical advantages, this review highlights the efficacy and applicability of these methods in the domain of heterocyclic chemistry, providing an invaluable framework for future drug discovery and development efforts. Full article