Abstract: Chalcone, a prominent scaffold, is well recognized for its anticancer properties. The overexpression of epigenetic regulatory enzymes such as histone deacetylases (HDACs) has been associated with tumour progression and cancer development. The role of the chalcone scaffold in the inhibition of HDACs has been explored over the years. This study investigated the research progress reported on HDAC inhibition by compounds with a chalcone scaffold and evaluated their potential in medicinal chemistry. The research articles were sourced from multiple databases, such as SCOPUS, Google Scholar and PubMed, via the keywords ‘chalcone’, ‘histone deacetylase inhibitor’, ‘HDACi’, ‘HDAC’ and ‘chalcone HDAC inhibitor’. The articles are classified into two main categories according to their structural features. First, HDAC inhibition is achieved via zinc chelation of the carbonyl functional group of the chalcone scaffold. Second, zinc chelation is shown by known zinc-binding groups (ZBGs), and the chalcone scaffold enhances the interaction with the target. In each category, there are subdivisions on the basis of the presence or absence of heterocycles, dual inhibition, and any other modifications. Chalcone compounds with hydroxyl (-OH) and methoxy (-OCH3) substituents have shown therapeutic relevance. Although the inhibition of HDACs by chalcone scaffold metal chelation has been shown, it is comparable to or less effective than known ZBGs, such as hydroxamic acids and benzamides. These findings increase the understanding of the ability of the chalcone scaffold to inhibit HDAC activity and explain its effect on cytotoxicity. Analysis of the influence of substituents offered insight into structural optimization. Further research on structural modifications may reveal improved metal chelation and enhanced cytotoxicity.
Abstract: Salicylanilide-based compounds represent a versatile class of bioactive molecules with broad therapeutic potential. Originally developed as anthelmintic agents, these compounds have subsequently attracted considerable attention due to their diverse pharmacological activities, including antimicrobial, anticancer, anti-osteoclastogenic, anti-obesity, cardiovascular, and neuroprotective effects. In recent years, extensive medicinal chemistry efforts have focused on optimizing the salicylanilide scaffold to improve biological activity, target selectivity, and pharmacokinetic properties. This review provides a comprehensive overview of the therapeutic applications of salicylanilide derivatives, emphasizing recent advances in their medicinal chemistry, mechanisms of action, and structure–activity relationships (SARs). Analysis of available SAR data reveals several recurring trends across different therapeutic areas. Biological activity is frequently enhanced by electronwithdrawing substituents on the anilide ring, while the phenolic hydroxyl group often plays a critical role in target engagement, although its importance may vary depending on the pharmacological application. In addition, strategic scaffold modifications, including carbamate and thiocarbamate derivatization, prodrug approaches, heterocycle incorporation, and ring-fused analogues, have been successfully employed to improve potency, selectivity, solubility, and bioavailability. Collectively, the available evidence highlights the salicylanilide scaffold as a promising platform for the development of novel therapeutics. The SAR insights summarized in this review provide a valuable framework for the rational design and optimization of next-generation salicylanilide-based drug candidates and support further in vivo and clinical investigations of this scaffold.
The field of heterocyclic chemistry is a vital area of medicinal chemistry, characterized by notable dynamism that helps develop many physiologically active drugs. The extensive presence of heterocycles in drugs, natural products, and biological intermediates underscores their importance in the development of contemporary drugs. Histamine is an important endogenous biogenic amine with various physiological and immunological roles, including the inflammatory response, gastric acid secretion, neurotransmission, and immune regulation. The physiological effects of histamine are mediated by its interaction with four types of histamine receptors (H1, H2, H3, and H4). Histaminergic agents are of significant therapeutic importance due to their involvement in various disorders through dysregulated activity. Antihistamines have found applications in the management of problems related to the stomach, allergies, and certain neurodegenerative disorders. These drugs act by blocking histamine receptors. The first- and second-generation H1 antihistamines continue to play an important role in treating motion sickness, urticaria, and allergic rhinitis, as well as other conditions associated with these conditions. However, modern analogues of these drugs are much safer and do not cause any sedation. This review discusses the diversity of heterocycles in antihistaminic drugs, their interactions with receptors, their medicinal value, and the medicinal chemistry approaches that have paved the way for the development of such antihistamines.
Abstract: Podophyllotoxin (PTOX), a plant-derived aryltetralin lignan, has long been appreciated for its strong cytotoxic and antimitotic properties. Various derivatives of PTOX, including etoposide and teniposide, are well-established chemotherapeutics, although their use is largely hampered by systemic toxicity, low solubility, and drug resistance. Recent developments in modern chemistry and cancer biology have led to growing interest in developing novel PTOX-derived compounds with improved efficacy and reduced toxicity. This review presents the molecular mechanisms underlying the antitumor activity of PTOX and its derivatives, with particular emphasis on the inhibition of tubulin polymerization and DNA topoisomerase II. Furthermore, the roles of key signaling pathways, including PI3K/AKT, NF-κB, AMPK/HIF-1α, and Chk2/Twist1/EMT, in mediating antitumor effects in breast, lung, liver, and colorectal cancers are highlighted. Recent strategies involving the incorporation of PTOX into nanoparticles, hybrid molecules, and other bioactive systems have expanded its therapeutic potential by improving solubility, pharmacokinetics, and tumor selectivity. Overall, understanding structural modifications and molecular interactions of PTOX derivatives provides a strong foundation for the rational design of more potent and targeted anticancer agents.
Parkinson's disease (PD) is an irreversible neurodegenerative disorder leading to movement disorders including trembling, rigidity, and bradykinesia. The majority of these symptoms result from the death of dopaminergic neurons in the substantia nigra. Despite various pharmaceutical and surgical methods like levodopa treatment and neuromodulation being applied, none of them prevent the progression of PD. Various factors, both genetic and environmental (pesticides, head trauma, mitochondrial dysfunction), contribute to the development of this disease. Recent studies demonstrate the potential of MAO-B inhibitors to prevent dopamine degradation and oxidative stress. Schiff base derivatives are among the most interesting novel structures due to their ability to provide neuroprotection, free radical scavenging, and enzyme inhibition. The studies on isatin, benzothiazole, benzimidazole, and coumarin Schiff bases proved their potent and selective inhibition of MAO-B. Some of them demonstrate nanomolar IC50 values and promising pharmacokinetic parameters, including BBB penetration. According to the SAR, substitutions (EWG (-NO2, -Cl, -Br) and hydroxyl) increase lipophility and affinity to MAO-B. Schiff base structures have been identified as potential multi-functional platforms for the development of novel agents for neuroprotection against the effects of motor impairment and non-motor dysfunction in PD patients.
Heterocyclic derivatives represent the primary scaffold for numerous medicinal agents of utmost importance for humanity. Among them, triazine derivatives, and particularly the s-triazine scaffold, have long represented a cornerstone in medicinal chemistry research due to their broad pharmacological versatility. This heterocyclic system is a key structure in the design of therapeutic agents exhibiting antitrypanosomal, antiviral, antimicrobial, anti-inflammatory, antidiabetic, and anticancer activities. The s-triazine core represents a privileged scaffold, allowing rational optimization through targeted substitution patterns at different positions. Indeed, the triazine ring is characterized by the replacement of 3 carbon atoms of a benzene ring with three nitrogens, affording three easily modified sites at positions 2, 4, and 6, which can be variously substituted to modulate physiological and biological activities. In this review, we will focus on the structural and pharmacological features of s-triazine-based compounds developed as anticancer agents. Indeed, cancer is an increasing worldwide emergency, and its incidence and mortality will double in the next twenty years. Thus, the development of innovative and powerful anticancer agents remains one of the biggest challenges in the research world. In this respect, we provide an overview of the recent primary literature concerning the development of s-triazine-based antitumor agents, focusing on the most potent compounds acting on specific molecular targets and discussing the structure-activity relationships (SARs), when available. The aim is to provide important principles for the future development of new anticancer agents with greater potency against drug-sensitive and drug-resistant cancers.
Artificial Intelligence (AI) is increasingly embedded within modern medicinal chemistry workflows, particularly across the Design-Make-Test-Analyse (DMTA) cycle, where critical decisions must be made under conditions of uncertainty. Rather than functioning as a stand-alone predictor, AI is best understood as a decision-support framework that assists chemists in selecting screening hits, prioritising analogues for synthesis, managing multi-parameter optimisation, and identifying developability and safety risks at early stages. This structured narrative review examines how contemporary Machine Learning (ML) and Deep Learning (DL) approaches are being applied at key decision points in small-molecule drug discovery, including virtual screening and hit triage, Structure-Activity Relationship (SAR) prioritisation, lead optimisation for Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) liabilities, and synthetic feasibility assessment through retrosynthesis planning. By integrating ligand-based and structure-based models, multi-task learning, active learning, generative design, and uncertainty-aware predictions, AI systems can reduce experimental burden while improving the quality of decisions made by medicinal chemists. However, the practical impact of these tools depends critically on appropriate validation strategies, applicability domain assessment, and probability calibration to avoid misleading confidence. Taken together, the evidence reviewed here supports models of AI-augmented medicinal chemistry, in which data-driven predictions and human chemical intuition jointly enable more efficient, transparent, and reliable progression from hits to optimised lead candidates.
INTRODUCTION/OBJECTIVE:Familial Pulmonary Fibrosis (FPF) is a lung disease, a subset of which is associated with mutations in telomere-related genes, causing breathing difficulties and compromising quality of life. Telomere length is maintained and extended by telomerase, a reverse transcriptase enzyme that uses an RNA template, generating repetitive sequences rich in guanosine. However, heterozygous loss-of-function mutations in the TERT gene result in telomerase haploinsufficiency, reducing enzyme activity and contributing to earlier disease onset. In this context, it is important to evaluate the potential effects of NRTIs on telomerase, particularly whether these drugs may inhibit its activity. This review discusses the potential implications of this interaction for patients with FPF. METHODS:This study is based on a narrative literature search conducted in the PubMed database, using combinations of the relevant keywords, regardless of their year of publication. RESULTS:A literature review identified studies investigating the effects of NRTIs on telomerase activity. Overall, the available evidence indicates that several NRTIs, depending on the study design and the specific molecule evaluated, may inhibit telomerase activity as an off-target effect, although a limited number of studies have reported conflicting findings. DISCUSSION:FPF patients with HIV or those receiving Pre-Exposure Prophylaxis (PrEP) are treated with Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs). This class of medications includes molecules such as tenofovir, which may exert an off-target inhibitory effect on telomerase. Through this inhibition, telomeres cannot be elongated, and given the reduced telomerase availability, progressive telomere shortening occurs. In cases of telomerase haploinsufficiency, this inhibition could lead to symptom progression and poorer prognosis. CONCLUSION:These findings suggest that caution may be warranted for patients with genetically confirmed telomere-related FPF who require NRTI therapy, considering the potential off-target effects of these drugs on telomerase. Further clinical and mechanistic studies are needed to clarify whether NRTI exposure influences disease progression and prognosis.
Molecular dynamics (MD) simulations have become an increasingly important component of modern medicinal chemistry and structure-based drug discovery, providing atomistic insight into protein-ligand interactions that extends beyond static experimental structures and docking models. By explicitly accounting for conformational flexibility, solvent effects, and time-dependent behaviour, MD simulations enable the refinement of binding poses, the identification of transient and allosteric sites, and the quantitative estimation of binding thermodynamics and kinetics, the latter increasingly accessible through Markov state models (MSMs) and milestoning approaches that reconstruct long-timescale behaviour from ensembles of short trajectories. In this mini-review, we provide a practical overview of classical atomistic MD methodologies commonly used in medicinal chemistry, including force-field-based simulations, enhanced sampling techniques, and free-energy calculation methods such as alchemical and end-point approaches. Emphasis is placed on the strengths and limitations of each technique, with particular attention to their appropriate use across different stages of the drug discovery pipeline. We further discuss best practices for system preparation, simulation protocol design, convergence assessment, and reproducibility, highlighting common pitfalls that can lead to overinterpretation of simulation results. Selected examples illustrate how MD simulations have informed medicinal chemistry decisions in lead identification and optimisation. Finally, we briefly outline emerging directions, including the integration of machine learning, ensemble-based approaches, and next-generation force fields, which are expected to further expand the role of MD simulations in medicinal chemistry.
Introduction: Viruses pose serious threats to public health, with frequent outbreaks of emerging and reemerging viral pathogens. Given the limitations of current antiviral therapies, the search for new control strategies is essential. In this context, chalcones have attracted great attention due to their structural versatility and a wide range of pharmacological activities, including antiviral effects. Methods: We conducted a literature review examining the antiviral applications of natural and synthetic chalcones validated in experimental assays and reported in articles published up to December 2025 in the PubMed, Web of Science, and Google Scholar databases. Results: Chalcones have shown antiviral activity against more than 15 viral species, including respiratory viruses and arboviruses, human retroviruses, DNA viruses, and the plant pathogen tobacco mosaic virus. Discussion: Structural modifications of the chalcone core influence their mechanisms of action, which involve diverse targets such as viral proteases, kinases, polymerases, structural proteins, as well as host cell pathways. Nevertheless, limited selectivity likely remains a major challenge hindering further development of these compounds. Conclusion: Overall, the structural versatility of chalcones, their broad-spectrum antiviral activity, and their diverse mechanisms of action highlight their strong potential as antiviral agents. Yet, further optimization and in vivo studies are essential to develop more potent and safer chalcone-based drug candidates.
Introduction: Off-label drug use (OLDU) is frequent in populations insufficiently represented in clinical trials, including pediatrics, rare diseases, and psychiatry. Although it broadens therapeutic options, uncertainty regarding safety and response remains a central concern. Physical chemistry properties influence drug distribution, target promiscuity, and exposure profiles in offlabel contexts. Because the biological processes that translate these intrinsic molecular properties into pharmacokinetic and pharmacodynamic phenotypes are modulated by genetic variability, pharmacogenomics may provide a complementary strategy for anticipating interindividual differences in safety and efficacy. Materials and Methods: This narrative review integrates pharmacogenomics (PGx) evidence from curated clinical resources (ClinPGx, CPIC, DPWG, and regulatory sources) with principles of medicinal chemistry, prioritizing mechanistic evidence linking genetic variability to drug response variability in commonly prescribed off-label therapies across selected therapeutic areas. Results: Across the therapeutic areas examined, several drugs with frequent off-label use were identified as having available pharmacogenetic information. A subset of these agents was further discussed, considering mechanistic considerations derived from medicinal chemistry principles. Discussion: Intrinsic molecular characteristics help explain biodistribution patterns and off-target effects observed during off-label prescribing. Gene-drug interactions involving metabolizing enzymes and transporters consistently influence drug response. Evidence specifically designed for OLDU remains limited. Conclusion: The convergence of medicinal chemistry and pharmacogenomics may offer a promising framework to enhance safety and precision in off-label prescribing. Although direct evidence in these settings remains limited, the established influence of genetic variation on drug pharmacokinetics and pharmacodynamics provides a biologically plausible rationale for exploring PGx-guided approaches in OLDU
INTRODUCTION:Vanillin, a phenolic aldehyde, is the primary component of the vanilla bean's ethanolic extract. Synthetic vanillin is now more commonly used as a flavoring in foods, beverages, and pharmaceuticals. Natural vanilla extract consists of several hundred derivatives, while artificial vanilla flavoring is often a synthetic ethanol solution of pure vanillin. The first commercial synthesis of vanillin began with eugenol, and today, it is made from guaiacol or lignin. METHODS:This narrative review aggregates and critically assesses available literature on vanillin and its synthetic derivatives. A thorough literature review was conducted using prominent scientific databases, including PubMed, Scopus, Web of Science, and Google Scholar, covering papers from 2000 to 2024, with a specific focus on recent research. Experimental and review studies concerning the synthesis, structural changes, pharmacological activities, toxicological features, and structure- activity connections of vanillin and its derivatives were systematically examined and analyzed. The review emphasizes the biological evaluations, modes of action, and therapeutic potential of vanillinderived drugs in various illness types. RESULTS:Comprehensive evaluation of vanillin and its derivatives revealed their broad pharmacological spectrum, including significant neuroprotective effects against neurodegenerative disorders such as Alzheimer's disease and potent anti-diabetic properties. In addition, Several vanillin derivatives demonstrated promising antimicrobial and anticancer activities, emphasizing their therapeutic potential. The review highlights that diverse synthetic strategies such as Schiff base formation, Azo-Schiff base reactions, Williamson ether synthesis, Steglich esterification, Claisen-Schmidt condensation, and Mannich or reductive amination reactions are effectively employed to design and modify vanillin structures. These synthetic methods target functional groups like hydroxyl, methoxy, and aldehyde moieties, enabling the generation of novel bioactive derivatives with improved pharmacological profiles. Aldehyde (CHO) groups in vanillin are more susceptible to substitution than other functional groups. DISCUSSION:Vanillin is a structurally versatile phenolic aldehyde with broad pharmacological potential. Structural modifications of its hydroxyl, methoxy, and aldehyde groups significantly enhance biological activities, including neuroprotective effects against Alzheimer's disease, anti-diabetic, antimicrobial, and anticancer properties. The aldehyde moiety plays a key role in synthetic diversification through reactions such as Schiff base formation, Mannich reaction, and Claisen-Schmidt condensation, enabling the development of potent bioactive derivatives. Although promising preclinical results highlight the therapeutic potential of vanillin-based compounds, further pharmacokinetic and clinical investigations are required to advance them toward drug development. CONCLUSION:Vanillin and its derivatives represent a versatile class of compounds with multifaceted biological activities and vast potential in drug discovery. Their structural modifiability through various synthetic approaches allows the development of new therapeutic agents with enhanced efficacy and specificity. Continued exploration of their chemistry and pharmacology could pave the way for innovative treatments in neurodegenerative, metabolic, microbial, and cancer-related diseases.
Mitochondria, often referred to as the powerhouses of the cell, play a pivotal role in maintaining cellular homeostasis through the regulation of energy production, redox balance, and apoptosis. Recent evidence highlights the significance of mitochondrial dynamics, fusion, fission, biogenesis, and mitophagy, enabling cells to adapt to changing physiological and environmental conditions. Dysregulation of these dynamic processes alters mitochondrial function, promoting metabolic reprogramming, evasion of apoptosis, and resistance to chemotherapy. Specifically, enhanced mitochondrial fission is often linked to increased metabolic flexibility and resistance to cell death, while aberrant fusion supports mitochondrial quality control under cellular stress. Additionally, tumour cells also exhibit bioenergetic flexibility, dynamically switching between OXPHOS and glycolysis to meet energy demands and overcome therapeutic stress. This metabolic change influences ROS levels, directly affecting the efficacy of anticancer agents in cancer cells. Such adaptations are now recognised as hallmarks of drug-resistant cancers. This review explores the mechanistic interplay between mitochondrial dynamics and cancer bioenergetics, emphasising how these processes contribute to drug resistance. We also focus on emerging therapeutic strategies, particularly smallmolecule inhibitors targeting mitochondrial fusion and fission that offer promising potential to restore chemosensitivity and disrupt cancer cell survival. A deeper understanding of mitochondrial behaviour in cancer may reveal novel therapeutic targets for the development of more effective and durable cancer treatments.
Asthma is a prevalent chronic respiratory disease that is still a major concern for the global population, and it has been estimated to affect no less than 400 million people in the year 2025, mostly affecting children. Symptoms include persistent inflammation in the airways, attacks of bronchospasms, and resulting wheezing, shortness of breath, and coughing. Although there have been highly effective therapies available for patients in the form of inhalers, there have been concerns associated with the current therapies, including a lack of targeting, the need for repeated dosing, and the potential for unwanted side effects. However, to address these challenges, emerging approaches have used new delivery systems, specifically pH-sensitive microparticles. During the attack, there is a pH imbalance due to inflammation and the secretion of excess amounts of mucus. pH-responsive microparticles (1-5 μm), formulated with biocompatible materials such as chitosan, PLGA, and Eudragit, have been shown to deliver drugs to the deeper respiratory tracts and provide a sustained drug release. Furthermore, the importance of pH-responsive microparticles has been introduced in this review, wherein it has been described how these particles are capable of reducing inflammation, reducing systemic distribution, and also recovering lung functions. pH-sensitive microparticles can improve patient compliance with treatment by allowing fewer doses to be taken. This is particularly promising, especially given the worldwide burden of asthma in developing countries, where effective, precise, and simple asthma control is needed.
Oxazole derivatives are important heterocyclic scaffolds in medicinal chemistry due to their broad biological activities. These five-membered aromatic rings containing oxygen and nitrogen exhibit antimicrobial, antiviral, anticancer, anti-inflammatory, antifungal, and antitubercular properties. Their favorable electronic features and structural rigidity enable strong and selective interactions with diverse biological targets. Recent advances in synthetic methodologies, particularly the van Leusen protocol using tosylmethylisocyanides (TosMICs), have enabled efficient and regioselective oxazole construction. Additionally, magnetically recoverable catalysts offer sustainable and recyclable approaches with improved yields and reduced environmental impact. These developments have expanded the chemical space of oxazole-based compounds, facilitating the design of drug candidates with enhanced pharmacokinetic and pharmacodynamic profiles. This review summarizes recent synthetic strategies, pharmacological activities, structure-activity relationships, and biosynthetic and mechanistic insights highlighting the significance of oxazole motifs in modern drug discovery.
Introduction: Cancer remains one of the most prominent causes of death, affecting millions of lives globally, thereby posing a significant disease burden. Heterocyclic scaffolds, particularly pyrimidines, have proven effective owing to their versatile activity across various cancer types. This review aims to provide an extensive compilation of pyrimidine-based hybrid molecules as promising anti-proliferative agents, highlighting their synthesis, multi-target capabilities, key signaling pathways, structure-activity relationships (SARs), molecular targets, and therapeutic potential against cancer cells. Methods: A comprehensive literature survey was conducted using PubMed, Elsevier, Google Scholar, ScienceDirect, ACS, RSC, and PubChem to identify relevant reviews and research articles published between 2020 and 2025. The collective study was analyzed to evaluate pyrimidine-based hybrid structural modification, molecular targets, anticancer mechanism, and pharmacological properties. Result: Pyrimidine-based hybrid molecules have demonstrated antiproliferative activity, with several derivatives demonstrating excellent inhibitory potency, enhanced target selectivity, and improved pharmacokinetic characteristics. Pyrimidine hybrids effectively modulate multiple oncogenic targets and signaling pathways, including PI3K/AKT, CDKs, EGFR, HSP90a, and HDAC, leading to cell cycle arrest and apoptosis and inhibiting tumor growth. Further SAR revealed that strategic substitution on the pyrimidine scaffold significantly increased bioavailability, reduced toxicity, and improved target selectivity. Discussion: The literature indicates that pyrimidine-based hybrid molecules have significant potential as multitargeted anticancer agents, addressing the limitations of conventional single-target therapies. Their structural diversity was shown to modulate multiple cancer-related signaling pathways. The study highlights their promising, valuable lead scaffold for the development of next-generation anticancer agents. Conclusion: Pyrimidine-containing hybrids emerge as a privileged scaffold in medicinal chemistry for the development of effective, multitargeted anticancer agents with improved pharmacological profiles and reduced off-target effects. Therefore, further structural optimization and mechanistic analysis, along with preclinical evaluation, suggest that pyrimidine-based molecules hold significant promise for cancer therapy.
Despite remarkable advancements, the treatment of breast cancer remains a serious challenge. In recent decades, extensive studies have been conducted to identify new therapeutic targets for the treatment of breast cancer. Among these therapeutic targets that have gained attention in recent years are lncRNAs. These molecules appear to affect proliferation, metastasis, and drug resistance in cancer cells by regulating multiple signaling pathways. Among the signaling pathways implicated in breast cancer, the PI3K/AKT/mTOR pathway is one of the most important. Given the frequent dysregulation of the PI3K/AKT/mTOR pathway in breast cancer, numerous recent studies have investigated its interplay with lncRNAs. Emerging evidence indicates that lncRNAs regulate the PI3K/AKT/mTOR pathway by modulating microRNA availability, influencing transcriptional programs, and serving as molecular platforms for chromatin-modifying complexes. This mini-review synthesizes recent evidence on lncRNAs targeting the PI3K/AKT/mTOR cascade in breast cancer, summarizing molecular mechanisms, functional consequences for proliferation, invasion, and therapy resistance, and available in vitro and in vivo evidence. Representative oncogenic lncRNAs (e.g., HOTAIR, DANCR, and LINC01133) and tumor-suppressive lncRNAs (e.g., MEG3 and ZFAS1) are discussed, together with their potential as therapeutic targets. Finally, the current challenges and future perspectives for integrating lncRNAtargeted approaches with PI3K pathway inhibition in breast cancer therapy are highlighted.
Ionised radiation plays a crucial role in various fields, including diagnostic imaging, radiotherapy, industrial processes, and scientific research. With the increasing use of ionising radiation, there is a growing need for effective shielding to minimise harmful exposure. Traditionally, leadbased shields have been used; however, they pose significant health and environmental hazards, particularly due to lead dust exposure, which is a major concern for healthcare workers. Consequently, alternatives such as polymer-based metal nanohybrids are emerging as promising options for radiation protection. This paper reviews the latest research on EMI shielding using polymer-based metal nanohybrids, with a particular focus on their applications in radiation shielding. It examines the influence of polymer matrix materials and the effects of polymer and filler particle sizes on the attenuation of radiation, including X-rays, gamma rays, and microwaves. Key materials discussed polymers (such as PMMA, PVDF), nanostructures (e.g., Bi2O3, ZnO, Fe2O3), and hybrid nanostructures (e.g., PMMA/GO, PVDF/BaTiO2, WC, BaFe12O19, NiFe2O4). The paper explores their structure, properties, and advantages for radiation shielding. The shielding efficiency of these materials is assessed by using parameters such as the mass attenuation coefficient, linear attenuation coefficient, half-value layer, tenth-value layer, and mean free path. Compared to conventional shielding materials, polymer-based metal nanohybrids offer superior performance due to the unique properties of nanoparticles, including enhanced attenuation coefficients, lightweight, ease of fabrication, thermal stability, and electrical conductivity. These characteristics make them more efficient and environmentally friendly alternatives compared to traditional lead-based shielding.
Ischemic stroke continues to be a predominant global cause of death and long-term disability, with therapeutic options remaining notably constrained. Against this challenging backdrop, iridoids—natural monoterpenoids abundantly present in various medicinal plants—have gained significant attention as prospective neuroprotective agents for ischemic stroke. This comprehensive review systematically consolidates preclinical evidence regarding the therapeutic potential of ten representative iridoids, namely catalpol, picroside II, oleuropein, morroniside, loganin, aucubin, geniposide, cornin, gentiopicroside, and swertiamarin, utilizing data from diverse experimental stroke models. Accumulated findings reveal that these iridoid compounds mediate multi-modal neuroprotective benefits primarily through the regulation of crucial pathological cascades, such as excitotoxicity, persistent neuroinflammation, oxidative stress, apoptotic pathways, and blood-brain barrier integrity disruption. From a mechanistic standpoint, iridoids exert their influences by modulating a spectrum of vital signaling pathways, including VEGF/PI3K/Akt, Nrf2/HO-1, NF-κB, MAPK, and Bcl-2. These modulatory activities contribute to enhanced angiogenesis and neurogenesis, facilitate microglial polarization toward the protective M2 phenotype, and effectively mitigate oxidative damage and neuronal apoptosis. Given their pleiotropic mechanisms of action, iridoids constitute a highly promising class of natural scaffolds for developing innovative multi-target therapeutics for ischemic stroke. To advance their translational potential, subsequent research should emphasize structural optimization and synthetic derivatization to improve potency and pharmacokinetics. Concurrently, exploring advanced targeted drug delivery platforms appears imperative to maximize their bioavailability and brain penetration, thereby facilitating the transition of iridoid-based candidates from preclinical research to clinical application.
Cancer remains a leading cause of mortality worldwide, necessitating the continuous discovery and development of novel therapeutic agents with improved efficacy and reduced toxicity. Heterocyclic compounds are privileged scaffolds in medicinal chemistry, and among them, the triazole ring system (1,2,3-triazoles and 1,2,4-triazoles) has emerged as a highly versatile and promising pharmacophore for anti-cancer drug discovery. This review is an attempt to bridge the gap between synthetic structural biology and translational oncology by systematically connecting the structure- activity relationships of novel triazole hybrids targeting Aromatase, VEGFR-2, IDO1, and Carbonic Anhydrase. We present a comprehensive overview of the recent advancements in the design, structure-activity relationships, and biological evaluation of triazole derivatives as potent anticancer agents. Triazoles are known to play an important role in modulating key oncogenic pathways (such as apoptosis induction, cell cycle arrest, angiogenesis inhibition, and metastasis suppression) by binding to various pharmacological targets. Here, we critically present the spatial configuration, such as the "tail approach" needed for carbonic anhydrase inhibition and the very specific heme-iron distances of the IDO1 pathway that govern the therapeutic promise. Clinical progress, toxicity, bioavailability, and resistance challenges have also been addressed. This review underscores the significance of triazole derivatives as multifunctional anticancer agents and provides insights into future directions for their development as targeted and potent chemotherapeutic agents. Although triazole derivatives are widely recognized as versatile, drug-like moieties, a critical research gap persists in understanding minor structural or electronic modifications near the triazole ring system to make the molecule target-specific and prevent liabilities due to non-selectivity.
