Mini Reviews in Medicinal Chemistry - Online First

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the formation of senile plaques and neurofibrillary fiber tangles. Studies have shown that increased regional iron loading in the brain, dysregulation of iron homeostasis in the body, oxidative stress, and protein and lipid oxidation are all involved in the pathogenesis of AD. Ferroptosis, an iron-dependent, lipid peroxidation-driven form of regulated cell death, is increasingly implicated in the pathological process of AD, and some new compounds targeting ferroptosis demonstrate therapeutic efficacy in both cellular and animal models of AD. Therefore, this article systematically summarizes recent advances in the role of ferroptosis in AD pathogenesis and highlights progress in targeting ferroptosis for AD treatment, providing insights for future therapeutic and preventive strategies.

There is an urgent need to develop effective antiviral treatments against SARS-CoV-2. Despite the availability of vaccines, drug discovery remains critical for combating emerging variants. Molecular docking studies have become a vital computational tool for identifying antiviral drugs capable of inhibiting different SARS-CoV-2 proteins. This review explores the role of metal complexes as promising viral inhibitors through in silico molecular docking approaches. The binding abilities of several coordination complexes derived from iron, copper, palladium, and zinc ions have been evaluated against major viral proteins such as the spike glycoprotein, RNA-dependent RNA polymerase (RdRp), and the main protease (Mpro), which are responsible for viral infection. Comparative docking studies of specific metal-based compounds with conventional antiviral drugs highlight their superior binding affinities and inhibitory potential. Furthermore, ADME (Absorption, Distribution, Metabolism, and Excretion) analyses, molecular dynamics simulations, and drug-delivery strategies are discussed to assess pharmacokinetics and therapeutic viability. Overall, this review emphasizes the importance of molecular docking in the rational design of metal complexes as antiviral agents and its relevance for developing effective therapeutic strategies to combat COVID-19.

Cancer continues to pose a worldwide health concern, requiring breakthrough therapeutic approaches that are both efficacious and minimally intrusive. Berberine, a natural isoquinoline alkaloid, has attracted considerable interest due to its various pharmacological features, particularly its strong anticancer effects. Nonetheless, its clinical application has been impeded by inadequate bioavailability, rapid metabolism, and systemic elimination. Recent breakthroughs in nanotechnology have mitigated these issues by creating BBR nanoparticles (BBR NPs), which provide increased solubility, precise delivery, and higher therapeutic efficacy. This paper extensively examines BBR and its nanoparticle forms for cancer treatment. The mechanisms of action, including apoptosis induction, tumour angiogenesis inhibition, antimetastatic effects, and oxidative stress modulation, are thoroughly examined. Essential synthesis approaches for BBR nanoparticles, including chemical reduction, green synthesis, and encapsulation in nanocarriers, are discussed together with their characterization methodologies. The report emphasizes comparative studies that illustrate the enhanced antitumor efficacy of BBR nanoparticles compared to free BBR in preclinical settings. Notwithstanding encouraging results, nanoparticle stability, scalability, and regulatory obstacles must be resolved for effective clinical translation. Future directions are examined, encompassing advancements in nanoparticle design and their prospective incorporation into personalized oncology. This review highlights the transforming potential of BBR and its nanoformulations as a novel therapeutic approach in cancer treatment.

Natural products (NPs) have long served as a rich inspirational source for drug discovery and development, offering diverse chemical structures and biological activities. Among these, topsentin, a marine alkaloid derived from marine sponges, has emerged as a promising scaffold due to its remarkable pharmacological properties and structural versatility. This review explores the significance of topsentin and its derivatives in drug discovery efforts. It discusses the diverse biological activities of topsentin and its analogs, including anticancer, antimicrobial, anti-inflammatory, and antiviral properties, highlighting their potential therapeutic applications. Moreover, it also focuses on the structural features of topsentin that contribute to its pharmacological profile, emphasizing its importance in the design and development of novel therapeutic agents. Structural modifications and synthetic strategies employed to enhance the pharmacological properties of topsentin derivatives are also discussed. Overall, this review underscores the significance of topsentin as a promising scaffold in drug discovery.

MicroRNAs (miRNAs) are integral to the regulation of gene expression pertinent to cardiovascular health, affecting various biological processes, such as cell adhesion, inflammation, and lipid metabolism. Certain miRNAs (miR-1, miR-133a, miR-133b, miR-208a, etc.) have been associated with a range of cardiovascular disorders, including atherosclerosis, arrhythmias, and myocardial infarction, indicating their potential utility as therapeutic targets and biomarkers. Nevertheless, the therapeutic application of miRNAs is constrained by their inherent instability and suboptimal cellular uptake, which can be attributed to their negative charge and vulnerability to degradation. To mitigate these challenges, a variety of delivery systems have been developed, encompassing both viral vectors (such as adeno-associated viruses, adenoviruses, and lentiviral vectors) and non-viral vectors (including liposomes and polymer nanoparticles). Besides, the integration of nanoparticles, extracellular vesicles, and a hydrogel system can enhance the stability, targeting, and efficiency of miRNA delivery. Furthermore, advanced systems, such as intelligent responsive delivery mechanisms and multifunctional joint delivery systems, are currently under investigation to improve therapeutic outcomes. Notably, studies exploring poly (β-amino esters) as a non-viral gene delivery vector have demonstrated potential in advancing gene therapy for cardiovascular diseases. This article reviews the role of miRNAs in cardiovascular disease pathogenesis and therapy, discusses recent progress in miRNA delivery strategies, and summarizes clinical challenges and highlights the critical need for continuous innovation in delivery systems to enhance treatment efficacy, ensure safety, and facilitate industrial scalability.

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.