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.

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.

Individuals diagnosed with inflammatory bowel disease (IBD) face a significantly heightened risk of developing colorectal cancer (CRC), primarily due to persistent intestinal inflammation that fosters neoplastic transformations across the colon. This narrative review delves into the potential of certain fruits, such as black raspberries, Amazonian açaí, apples, grapes, cocoa, Ziziphus jujuba, and Moringa oleifera, in mitigating IBD-induced CRC. Preclinical studies indicate that these fruits possess anti-inflammatory and antioxidant properties that may disrupt carcinogenic pathways. Notably, black raspberries have demonstrated the ability to modulate epigenetic markers by demethylating tumor suppressor genes and inhibiting DNA methyltransferases (DNMT), like DNMT1 and DNMT3B. This epigenetic modulation influences the Wnt signaling pathway, crucial in CRC development, and affects cellular processes, such as proliferation, apoptosis, and angiogenesis. Animal models further support these findings, showing that black raspberries can suppress β-catenin signaling, reduce chronic inflammation, and decrease tumor incidence. This comprehensive analysis underscores the promising role of specific fruits in CRC prevention among IBD patients and highlights the need for further research to translate these findings into clinical applications, potentially benefiting both public health and the nutraceutical industry.