Mini Reviews in Medicinal Chemistry - Online First

Neem gum, a biocompatible and biodegradable polysaccharide, has broad applications in drug delivery and tissue engineering. Its hydrophilic and bioadhesive properties make it ideal for controlled drug release and scaffold fabrication. This review examines the role of neem and its derivatives in pharmaceutical formulations, wound healing, and regenerative medicine, while addressing stability, scalability, and regulatory considerations. Future directions include the integration of nanotechnology and chemical modifications for enhanced biomedical applications. Neem gum has been developed into various forms, including hydrogels, nanoparticles, films, and coatings, for targeted drug delivery and tissue regeneration. Its antimicrobial, antioxidant, and anti-inflammatory properties enhance wound healing and infection control, but challenges like batch variability and mechanical limitations remain. Neem gum is a promising natural biomaterial for pharmaceutical and biomedical applications. Further research on stability, large-scale processing, and clinical validation is essential for commercialisation and clinical use.

Stress granules (SGs) are membraneless cytoplasmic condensates formed through liquid-liquid phase separation (LLPS) in response to diverse cellular stressors. These dynamic macromolecular complexes serve as critical signaling hubs that orchestrate adaptive responses by sequestering translationally stalled mRNAs, RNA-binding proteins, and key signaling molecules. Substantial evidence implicates SGs in the pathogenesis of numerous disorders, where they dysregulate essential cellular pathways, including stress-induced cell death cascades. While regulated cell death constitutes a physiological process vital for tissue homeostasis, aberrant or excessive cell death represents a pathogenic driver in neurodegeneration, ischemic injuries, autoimmune disorders, infectious diseases, and oncological pathologies. Consequently, deciphering the molecular governance of cell death holds great potential for developing novel therapeutics. Although proteomic analyses reveal that SGs sequester multiple cell death regulators, the precise mechanisms through which these components modulate death pathways remain incompletely resolved. This review systematically examines the causal relationships between SGs dynamics and major cell death modalities, including apoptosis, necroptosis, pyroptosis, and ferroptosis. By synthesizing recent advances in SG biology and cell death regulation, we elucidate how stress-adapted SG proteomes functionally contribute to death pathway activation or suppression. This mechanistic synthesis not only resolves current controversies regarding SGs’ function in different cell death models but also identifies targetable vulnerabilities at the SGs-death pathway interface, offering innovative frameworks for treating SGs-associated pathologies.

Anthelmintic resistance in livestock is an escalating global concern, as synthetic anthelmintics tend to lose their efficacy within 2–10 years of their routine usage. This rapid development of resistance results in significant economic losses and threatens the sustainability of livestock production systems. Gastrointestinal (GI) parasitism, a primary health challenge in ruminants, significantly impairs productivity, fertility, and overall animal welfare. Environmental factors such as high humidity, temperature fluctuations, and poor management practices further predispose animals to certain parasitic infections. In recent years, the search for alternative solutions has led to a growing interest in plant-derived anthelmintics. These botanical compounds, rich in bioactive phytochemicals, offer a promising and eco-friendly approach to controlling parasites by targeting their metabolism, reproduction, and structural integrity. Unlike synthetic drugs, herbal anthelmintics are often associated with fewer side effects, reduced toxicity, and a lower risk of developing possible resistance. Several medicinal plants, such as Azadirachta indica, Allium sativum, Artemisia absinthium, and Fumaria parviflora, have demonstrated potent anthelmintic properties in both in vitro and in vivo studies.

Furthermore, synergistic effects among multiple phytochemicals can enhance efficacy and broaden the spectrum of activity against diverse helminths. This review highlights the efficacy, mechanisms of action, and practical applications of herbal remedies in controlling parasitic infections in ruminants. Emphasizing the integration of natural remedies into sustainable livestock health programs, this approach holds great potential to reduce reliance on synthetic drugs while improving animal health, productivity, and farm profitability.

Lung cancer remains a significant contributor to cancer mortality for several reasons. First, lung cancer is a molecularly heterogeneous disease. When combined with the dramatic resistance to treatment mediated by a tumor microenvironment (TME) that is inherently immunosuppressive, this explains the continued high mortality associated with lung cancer. The new era of treating non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), as well as achieving long-lasting treatment responses, is driven by immune checkpoint inhibitors (ICIs) targeting PD-1, PD-L1, and CTLA-4. This treatment revolution may, in the future, be applied to isolated cases of relapse and recurrent disease, resulting in sustained therapeutic responses.

In this review, we outline recent advances, including novel agent combinations and combination regimens tested in clinical trials that have become milestones, such as Nivolumab, Pembrolizumab, Durvalumab, and emerging bispecific combinations. Targeted therapeutic delivery is now possible through nanotechnology and biomaterials, such as polymer nanoparticles and smart hydrogels, which allow high local drug concentration at the tumor site while reducing systemic toxicity.

Predictive biomarkers, including PD-L1 expression, tumor mutational burden (TMB), circulating tumor DNA (ctDNA), and radiomic features, are increasingly used to select patients and assess treatment responses in real time. Despite these advances, resistance to immunotherapy and immune-related adverse events (irAEs) remain major challenges, emphasizing the need for ongoing innovation in personalized management, toxicity mitigation, and treatment strategies.

Industry leaders are now exploring artificial intelligence to optimize treatment selection and predict adverse events and outcomes early. Ultimately, improved survival rates and enhanced patient experiences may be achieved through the integration of novel biomarkers, precision technologies, and more effective immunotherapies for lung cancer patients. Significant research is still required to overcome resistance mechanisms, optimize combination therapies, and enable individualized care in this rapidly advancing field.

Despite recent advances in both preclinical and clinical cancer therapies, the growing problem of treatment resistance remains one of the most critical challenges in oncology. To overcome the drawbacks of current oncologic treatments, there is a pressing need for new approaches and potential therapeutic strategies. The interaction between the host microbiome and cancer has recently attracted significant research. Among the various routes of microbiome-cancer interaction, microbiome-derived exosomes also offer an intriguing avenue. Exosomes, which are small extracellular vesicles, originate from several distinct types of cells, including microbiome-associated cells. These vesicles participate in intra- and intercellular communication as well as alteration of the tumour microenvironment. Emphasising their possible functions as treatment response modifiers and mediators, this review seeks to explain an intricate link between cancer therapy resistance and exosomes produced from the microbiome. Preclinical studies reveal that microbiome-derived exosomes operate through horizontal transfer of resistance-conferring enzymes and TLR4/MYD88-dependent signalling, demonstrating 2-5 fold upregulation of resistance-associated miRNAs in drug-resistant models. Clinical evidence shows Akkermansia muciniphila improves anti-PD-1 immunotherapy outcomes. Fusobacterium nucleatum-derived vesicles promote oxaliplatin resistance through autophagy activation. We investigate how microbiota-derived exosomes might leverage resistance to conventional cancer treatments and their consequences for these treatments. However, limitations include inter-individual microbiome variability, challenging isolation protocols, and regulatory hurdles under FDA guidelines. We examine the possible applications of microbiome-derived exosomes as therapeutic and diagnostic tools, thereby reflecting the applicability of these findings in clinical practice. This offers an interesting path for new therapeutic approaches meant to solve treatment resistance and raise patient survival.

Imidazo[2,1-b][1,3,4]thiadiazoles, a class of fused bicyclic heterocycles, have garnered significant interest in medicinal chemistry due to their diverse biological activities, particularly their anticancer properties. Over recent decades, extensive research has been conducted to explore and enhance their therapeutic potential. This comprehensive review spans six decades of research on the imidazo[2,1-b][1,3,4]thiadiazole scaffold, focusing on structural variations at C-2, C-5, and C-6 position on this scaffold and their implications for anticancer activity. Modifications at these positions have been shown to significantly impact the compound’s efficacy against various cancer cell lines. Continuous exploration and optimization of these substitutions hold promise for the development of novel anticancer therapeutics.

Chronic Obstructive Pulmonary Disease (COPD) is a respiratory condition defined by persistent bronchitis, emphysema, and structural remodelling. The number of cases has risen globally; however, limited viable remedies exist. It is linked to airway blockage, oxidative stress, chronic conditions, inflammation, excessive mucus production, and increased autophagy and cellular senescence. Beta-2 adrenergic receptors (β2-ARs) play a significant role in both the aetiology and management of COPD. Beta-2 agonists (particularly long-acting beta-agonists, or LABAs) are preferable in COPD therapy due to their powerful bronchodilation, rapid onset, prolonged duration, and potential synergistic effects with other medications. They are well-tolerated and effective in improving the quality of life and reducing exacerbations, making them an essential component of COPD treatment. Currently, there are fewer bronchodilators that have been found to be effective. This leads to an exploration of novel, long-acting, and ultra-long-acting drugs for the management of COPD.

This article provides an extensive overview of natural β2 agonists. The current study emphasizes the rational development of lead candidates, including trantinterol, isopropyl, tert-butyl, and heterocyclic ring 2-amino-2-phenylethanol derivatives, 8-(2-amino-1-hydroxyethyl)-6-hydroxy-1,4-benzoxazine-3(4H)-one derivatives (non-substituted, methyl-substituted, dimethyl-substituted), 5-(2-amino-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one analogues, indacaterol analogues, saligenin antedrugs, and saligenin alkoxyalkylphenyl sulfonamide derivatives, accompanied by molecular docking studies. This paper also highlights numerous structure-activity relationship investigations and various novel β2 agonists currently in clinical trials and patents. The present review will significantly aid in fostering the research of COPD.

Three-dimensional (3D) printing is a transformative technology that has significantly influenced multiple sectors, including aviation, defence, architecture, and, more recently, healthcare and pharmaceuticals. Despite its growing adoption, there remain gaps in consolidated knowledge regarding its material versatility, regulatory considerations, and real-world implementation in clinical and pharmaceutical settings. Challenges related to biocompatibility, scalability, and the standardization of printed products hinder its full integration into medical practice. Addressing these issues requires a comprehensive understanding of the technological foundation, materials, and evolving applications of 3D printing in medicine. This review aims to provide an in-depth analysis of current advances, limitations, and prospects of 3D printing in healthcare. A systematic literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar databases, focusing on peer-reviewed articles published between 2010 and 2024. The review highlights key fabrication techniques, material innovations, clinical applications, and integration with emerging technologies, addressing critical challenges and opportunities for advancing personalized medicine.

Inflammatory Bowel Disease (IBD), which includes ulcerative colitis and Crohn’s disease, accounts for chronic inflammation in the entire gastrointestinal tract. Conventional treatments, such as amino salicylates, corticosteroids, immunomodulators, and biologics, can all alleviate symptoms; however, they may cause unwanted side effects and are extremely expensive. Most of the time, long-term treatment is also less effective. This review aims to discuss natural products (NPs) with therapeutic potential for IBD, emphasizing flavonoids, terpenoids, polysaccharides, and alkaloids. The compounds have been chosen based on literature reporting anti-inflammatory, antioxidative, and immunomodulatory activities that relate to IBD pathophysiology. Preclinical evidence using in vivo and in vitro models and available clinical data provides the basis for the main pharmacological effects, mechanisms of action, and safety profiles of these NPs. The key molecular pathways that are targeted include the NF-κB, MAPK, and JAK/STAT signaling pathways, as well as the establishment of the gut microbiota and intestinal barrier functions. Standardization, bioavailability, and maximal dosing remain challenging issues even when experimental models show promising results for various NPs. Hence, this review stresses the urgency for well-designed clinical trials and suitable formulation approaches to translate these observations into efficacious and evidence-based therapies. Being a natural remedy option, NPs could be considered complementary or alternative treatments for IBD, demanding further interrogation within an integrated therapeutic paradigm.

Neurological disorders (NDs) are diseases that arise due to deformities mainly in the central nervous system (CNS) and also affect the nerves throughout the human body. NDs, including Alzheimer’s disease (AD), Parkinson′s disease (PD), Multiple Sclerosis (MS), and a variety of brain malignancies, pose a major healthcare challenge and are the main cause of mortality on the global scale. There are very limited treatment options for the majority of the NDs, and the currently available drugs commonly fail to penetrate the BBB and deliver the drug to the target effectively. These challenges have necessitated the advent of new drug delivery methods that can cross the BBB with ease and deliver the drug by accurately targeting the diseased area in a safe and biocompatible manner. Nanoparticle-based drug delivery strategies offer significant advantages in BBB penetration and drug delivery due to their unique properties. Carbon dots, among nanoparticles with a size below 10 nm, are highly biocompatible, fluorescent molecules that offer ease of functionalization, drug conjugation, and effective detection within biological systems. The literature is rich in reviews on the synthesis, characterization, and application of CDs. However, a review specifically focused on the therapeutic potential of CDs in major NDs is missing. This review aims to fill that gap by presenting a detailed account of the carbon dot-based therapeutic approaches in the treatment of major NDs. It briefly discusses the properties of CDs, the main routes of synthesis, major raw materials, and key synthesis parameters that affect their properties, while placing a greater emphasis on their therapeutic potential. The review provides a detailed assessment of literature from the past 15 years on the development and current challenges in the application of CDs as therapeutic and drug delivery agents. Our analysis reveals that limited research has been conducted on CD-based therapeutics in NDs, particularly in MS and brain tumors, where original research is scarce. This review article highlights the major developments in the therapeutic uses of carbon dots in NDs, addresses a critical research gap, and provides a comprehensive overview of various studies related to carbon-dot-based therapeutic approaches for major NDs.

Mitochondria, commonly termed the 'cellular powerhouse', produce the majority of cellular adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). In addition to their role in energy synthesis, mitochondria are crucial for maintaining calcium homeostasis, mediating cellular signaling, regulating cell proliferation and apoptosis, and supporting various other physiological processes. In recent years, mitochondria have gained prominence as a critical target for the treatment of metabolic disorders. Research has demonstrated a strong association between mitochondrial dysfunction and the pathogenesis of metabolic diseases, such as insulin resistance, diabetes, metabolic syndrome, cardiovascular diseases, and endocrine tumors. Consequently, understanding the mechanisms of mitochondrial homeostatic imbalance and developing mitochondria-targeted therapeutics hold promise for innovative treatments of metabolic disorder-related diseases. This article seeks to elucidate recent advancements in the understanding of mitochondrial dysfunction's role in metabolic diseases and offers a comprehensive overview of current therapeutic strategies and approaches for addressing this dysfunction.

Magnetic liposomes (MLs) are hybrid nanovesicles that combine the biocompatibility of lipid bilayers with the remote controllability of superparamagnetic nanoparticles. To the best of our knowledge, no prior review has systematically covered the literature on MLs published between 2020 and 2024, with a special focus on continuous‐flow microfluidic synthesis. Here, we consolidate and critically assess recent advances in MLs’ structural design, highlight remaining challenges, and propose future directions for clinical translation. MLs, as one of the types of biomimetic magnetic nanovesicles, are considered promising nanocarriers for biomedical applications. These applications include active drug targeting to specific tissues, magnetic resonance imaging, magnetic hyperthermia, controlled release, and other applications. This review aims to comprehensively classify current knowledge on the main structural types of MLs and their traditional (batch) and modern (continuous‐flow) synthesis methods. The current advantages and potential challenges of microfluidics-based MLs synthesis are described. Detailed information on the variants of microfluidics-based techniques is provided, along with examples and potential biomedical applications. For the main aspects of MLs synthesis and applications, schematic illustrations are provided. Finally, an outlook on the perspectives of further MLs development and applications is presented.

Musculin antisense RNA 1 (MSC-AS1) is a long non-coding RNA (lncRNA) located on human chromosome 8q13.3-q21.11. Emerging evidence shows that MSC-AS1 is either upregulated or downregulated in 16 types of human cancers, and is associated with clinical pathological features and patient prognosis in 12 of these cancers. It is widely believed that the dysregulation of MSC-AS1 contributes to tumor cell growth, metastasis, epithelial-mesenchymal transition (EMT) progression, metabolic reprogramming, and drug resistance formation. Mechanistically, MSC-AS1 can act as a competing endogenous RNA (ceRNA) by sponging 14 miRNAs to affect the expression of downstream mRNAs, or it may directly interact with proteins, both of which contribute to the activation of the PI3K/AKT and Wnt/β-catenin signaling pathways. Our review study suggests that MSC-AS1 is a potential cancer biomarker and therapeutic target. In summary, we have explained the research on MSC-AS1 related to cancer treatment, its expression patterns, functional characteristics, and molecular mechanisms in malignant tumors. We have further emphasized its significance in clinical prognosis and therapeutic applications.

Artificial Intelligence (AI) is emerging as a valuable tool in pharmaceutical formulations, including the development of effervescent tablets (ETs). This review highlights how AI techniques are being explored to support ET formulation designs, optimize component ratios, predict disintegration and dissolution behavior, and control reactions through artificial neural networks, support vector machines, and machine learning. These techniques have been applied in recent studies to enhance stability, improve disintegration times, and flavor masking. Computational fluid dynamics simulations of effervescence and dissolution are underexplored for ETs. Data-driven approaches, like response surface modeling, require ingredient concentrations, tablet properties, consumer preferences, and predictive analytics for optimization. However, limited comprehensive datasets, complex reactions, environmental sensitivities, and ethical/regulatory considerations pose challenges. Overcoming these obstacles, as identified in the current literature, could enable AI to innovate ET development and personalization.

Recent trends have shown the development of various medicinally important compounds that specifically target B-cell receptor (BCR) pathways at various segments that have a major role in Bruton’s tyrosine kinase (BTK) receptor, which belongs to the family of kinases. These kinases are usually situated close to the cell membrane due to which they participate in upstream processing of BCR signalling. Various molecules have been potentialized to target these signalling pathways of these kinase receptors in order to achieve a pharmacological effect. Given the central role of BTK in immunity, BTK inhibition represents a promising therapeutic approach for the treatment of multiple diseases. BTK inhibitors work by regulating B-cell receptor signalling along with inflammatory pathways and immune cell interactions, offering more advanced treatment options compared to traditional therapies. In addition to BTK inhibitors, an extensive knowledge of the pharmacological mechanisms underlying the blockage of these receptors is necessary in order to more accurately forecast when and where a patient could need combination therapy or just one medication. Efforts have been made to facilitate translational discoveries, drug re-purposing concepts, and further development of precision medicine products. This thorough literature study has focused on studies published until June 2025.

Inflammation is a key contributor to the pathophysiology of various chronic diseases, including cancer, arthritis, cardiovascular disorders, chronic wounds, and gastrointestinal conditions, many of which rank among the leading causes of mortality worldwide, according to the WHO. The prevalence of chronic inflammation-related diseases is projected to rise steadily over the next 30 years, with an estimated three out of five individuals dying daily as a result of such conditions. Consequently, there is a growing demand for the discovery of novel anti-inflammatory agents. Cyclooxygenases play a pivotal role in inflammatory processes, being responsible for the synthesis of prostaglandins.

COX-1 is constitutively expressed and primarily associated with “housekeeping” physiological functions, whereas COX-2 is an inducible isoform involved in inflammatory responses. Due to its role in inflammation and relatively favorable gastric safety profile compared to traditional NSAIDs, COX-2 inhibitors have emerged as a significant therapeutic target for inflammation-related disorders. However, the increased risk of stroke and heart attack associated with COX-2 inhibitors has led to the withdrawal of several approved COX-2-targeting drugs from the market. Consequently, the development of new COX-2 inhibitors with potent efficacy and minimal cardiovascular side effects is of critical importance. This review explores a range of oxygen- and nitrogen-containing heterocycles as potential anti-inflammatory agents, emphasizing their COX-2 inhibitory activity, structure–activity relationships, and interactions within the COX-2 active site, as reported in recent studies. The article covers research findings published from 2019 through the first quarter of 2025.

Millions of people worldwide are affected by neurodegenerative disorders (NDs), which include a broad range of clinical ailments that affect the brain or peripheral nervous system, including Alzheimer’s disease (AD), Parkinson's disease (PD), Huntington's disease, etc. Neuronal cell death in NDs is often linked to oxidative stress; thus, antioxidant treatment can combat oxidative cell damage, and this strategy has been studied in neurodegenerative processes. Over the past 10 years, we have witnessed intense research activity on the biological potential of human monoamine oxidase (hMAO) inhibitors that have been associated with the prevention of oxidative stress and inflammation. These inhibitors have emerged as promising therapeutic agents, especially in the treatment of neurodegenerative diseases (NDs), where their core activity may help mitigate disease progression. An overview of the current state of numerous scaffolds, such as chromones, coumarins, chalcones, propargylamines, benzothiazoles, aminoisoquinolines, and the natural compounds, including ferulic acid, resveratrol, and chrysin, which combine antioxidant capability and hMAO inhibition is given in this review, with particular attention given to each scaffold's mechanism of action and structure-activity relationships (SARs), which are thoroughly discussed. Focusing on the dual mechanism of action, combining inhibition and antioxidant properties, as a potential therapy for neurodegenerative diseases, we have reviewed the different chemical classes of multi-target-directed ligand (MTDL) inhibitors developed within this framework. Other central nervous system (CNS)-related enzymes, such as cholinesterases, carbonic anhydrases, and BACE-1, have also been explored as targets in the MTDL strategy. By understanding their biological activity, medicinal chemists can better comprehend biological activity and recommend more effective and specific ND treatments.