Current Topics in Medicinal Chemistry - Online First

Betanin is widely consumed around the globe either as beetroot directly or as one of the key ingredients in food and pharmaceutical preparations. The health benefits of Betanin, including the treatment of numerous neurological diseases and brain cancer, have been reported extensively. Betanin has gained global attention due to notable anti-inflammatory, antioxidant, and anti-cancer activities. Recently, there has been growing attention on the usage of Betanin to prevent or delay the onset of neurodegenerative disorders. This review recapitulates available information from various recent pre-clinical studies on Betanin in several neurological diseases, such as Parkinson's disease, Alzheimer's disease, aging, brain stroke, anxiety, and neuropathic pain. Betanin exhibits remarkable neuroprotective effects via activation of the Nrf2 signaling pathway, inhibition of the production and expression of pro-inflammatory mediators and reactive oxygen species, along with suppression of the NF-κB signaling pathway. Taking betanin as part of a healthy diet may aid in the management of various brain-related disorders. This review focuses on the neurological conditions for which betanin has shown therapeutic potential, highlighting its beneficial properties, cellular and molecular mechanisms of action, and its relevance in light of current research. Based on the available evidence, betanin could be considered a promising candidate and lead compound in the drug development process for the prevention, treatment, and management of several neurological disorders in the future.

Neurodegenerative disorders (NDDs) are a major global health concern and the fifth leading cause of death worldwide. Huntington's disease (HD) is an NDD regarded as a rare, genetic, and advanced disease that occurs due to the duplication of cytosine, adenine, and guanine (CAG) trinucleotide repeats on chromosome 4p, located in the Huntingtin gene (HTT). There is no specific therapy available for HD. This review examines current evidence on various nutraceuticals as therapeutic or preventive agents in HD and their benefits in protecting against neuronal damage, oxidative stress, mitochondrial dysfunction, and combating excitotoxicity and neuroinflammation. Moreover, the beneficial role of nutraceuticals in HD involves averting defective energy metabolism, protein misfolding and aggregation, and epigenetic modulation, as well as strengthening cognitive and behavioral health. Nutraceuticals are naturally derived, bioactive components generally available in foods, dietary supplements, and herbal products, and they contribute to health promotion and disease prevention. These nutraceuticals possess potent antioxidant, anti-inflammatory, and neuroprotective properties, which help minimize the risk of HD. Moreover, antibacterial, antiviral, antimicrobial, anticancer, antiaging, antidiabetic, antihyperlipidemic, and immunobooster characteristics attract a large population worldwide. The wide availability of nutraceuticals in fruits, vegetables, and several naturally occurring foodstuffs supports their accessibility. These nutraceuticals function by stabilizing mitochondrial function, counteracting calcium overload, minimizing oxidative stress, and preventing inflammatory responses, among other mechanisms. The wide acceptance and demand for these nutraceuticals are due to their multifunctional role, economic benefits, and safety profile. The most promising nutraceuticals in the prevention and therapy of HD discussed are Curcumin, Resveratrol, Quercetin, Epigallocatechin Gallate, Hesperidin, Coenzyme Q10, Kaempferol, Silymarin, Astaxanthin, Lycopene, and Rosmarinic acid.

Cancer is a widespread disease that often causes severe pain, significantly reducing patients’ quality of life and increasing the overall burden of the illness. Managing cancer pain effectively remains a major clinical challenge. Metabolism is a fundamental biological process that involves both the breaking down of substances to produce energy (catabolism) and the building of complex molecules (anabolism). Cancer cells exhibit altered energy metabolism, including glycolysis, oxidative phosphorylation, glutamine metabolism, and lipid metabolism. Emerging research suggests that these metabolic changes can amplify cancer pain through specific signalling pathways, such as AMPK and PI3K/AKT. Targeting these metabolic pathways offers a promising approach for pain relief. This review explores the link between cancer pain and energy metabolism, highlighting potential new therapeutic strategies aimed at metabolic targets.

Treatment of neurodegenerative diseases aims to slow disease progression, alleviate symptoms, and improve life quality. Adipose-Derived Stem Cells (ADSCs) have emerged as a promising treatment for neurodegenerative diseases that can be easily obtained from adipose tissues. Their abundance, accessibility, and potential for multilinear differentiation make them an attractive candidate for regenerative medicine. ADSCs can release neurotrophic factors, modulate neuroinflammation, and potentially differentiate into neurons, giving hope for neuronal repair and replacement. Preclinical studies have shown the efficacy of several neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and spinal cord injuries. ADSC has demonstrated the potential to improve functional results, promote neurogenesis, induce tissue integrity, and reduce neuron loss. Clinical trials are still underway, but evidence of the effectiveness of ADSC in neurodegeneration is still being developed. The first clinical studies focused on safety and feasibility and achieved promising results. Optimizing cell transmission, controlling tumor growth, standardizing treatment protocols and such challenges remain. Current research is aimed at addressing these obstacles and transforming ADSC therapy into a widespread clinical practice. This review focuses on the characteristics, problems, and future approaches of ADSC in the context of neurodegenerative diseases and therapeutic processes.

Oxidative stress plays a critical role in many diseases, making it essential to study its impact on disease progression. However, clinical trials have many limitations and, in some cases, may not be possible at all. In this case, the development of in vivo models is highly anticipated. This is especially relevant for neurodegenerative diseases. Drosophila melanogaster models have a number of advantages over many other animal models, including the availability and cost-effectiveness of breeding, the accumulated knowledge of the Drosophila genome, and the ability to manipulate a large number of individuals. The latter allows for rapid screening and in-depth studies of potential therapeutic agents, including natural compounds with antioxidant activity. This review describes genetic models of such pathologies as Parkinson’s disease, Huntington’s disease, Alzheimer’s disease and hereditary spastic paraplegia created on Drosophila melanogaster. Studies conducted on such models are presented with an emphasis on the role of oxidative stress analysis. Oxidative stress is proven to be a link between neurodegenerative and metabolic diseases. In addition, studies on Drosophila melanogaster have been analyzed, in which the prospects of natural compounds as therapeutic agents for neurodegenerative and metabolic diseases have been demonstrated.

Lung cancer continues to be a leading cause of cancer-related mortality worldwide, underscoring the urgency for innovative and targeted drug discovery strategies. This review critically explores the role of Quantitative Structure-Activity Relationship (QSAR) modelling, particularly its integration with artificial intelligence (AI), in accelerating the identification and optimization of lung cancer therapeutics. Recent progress in multi-target approaches, machine learning (ML) algorithms with mathematical representations, and molecular descriptor engineering has been analyzed, with a special focus on clinical translations. Rather than offering a generic overview, we evaluate how AI-powered QSAR addresses key bottlenecks in drug development, such as data imbalance, model interpretability, and ADMET prediction failures. Notable case studies are examined to highlight translational success stories in lung cancer-specific pathways. This review offers a cohesive synthesis of current advancements, identifies critical gaps and limitations, and proposes future directions for enhancing the real-world applications of QSAR methodologies in oncological drug discovery.

Pharmacodynamic interactions are relevant in improving drug efficiency without a significant increase in the effects due to toxicity and, in most, are associated with polypharmacy. Mechanisms that govern pharmacodynamic interactions are additive, synergistic, and also antagonistic. Additive drug interactions refer to effects similar to a summation of effects resulting from administering a pair of drugs or a series, while synergistic describes a heightened response much above what one might have aspired to in light of expectations about additivity. However, the antagonistic effect may weaken therapeutic activity at times. Mechanistic pathways like receptor binding, enzyme inhibition, and modulation of signaling pathways were also studied to bring out their relevance in clinical applications. The manuscript is conscious of the role of patents and clinical trials in understanding pharmacodynamic interactions. Patents provide insight into new drug combinations and mechanisms, and the same interaction gets validated through the outcome of clinical trials. Examples that prove clinical relevance have emerged through the synergy in the usage of the drugs for oncology, cisplatin and etoposide, or the additive effect of aspirin and clopidogrel in preventing thrombotic events. The transformative approaches applied in developing drugs include network pharmacology, epigenetics, and receptor crosstalk. In this review, the pharmacodynamic interactions, by integrating mechanistic insights with clinical data, patents, and case studies, explicitly underpin pharmacodynamic interactions as a factor that enhances drug safety, efficacy, and therapeutic precision.