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Current Topics in Medicinal Chemistry - Volume 26, Issue 2, 2026

Volume 26, Issue 2

Volume 26, Issue 2, 2026

    • Neurological Inflammation in Parkinsonism: Current Prognosticative Diagnostics and Pitfalls

      https://doi.org/10.2174/0115680266365134250530063901

      Parkinson's disease (PD) is a persistent neurological degenerative condition that can significantly alter one's quality of life. This condition affects the substantia nigra, the region of the brain that contains dopamine-producing neurons. It is a disorder of the central nervous system that arises when nerve cells, or neurons, in this brain area are damaged or die. Norepinephrine, another chemical messenger that aids in controlling primary physiological processes, such as heart rate and blood pressure, is also deficient in PD patients. The symptoms of PD can interfere with daily activities and include fatigue, walking difficulties, limb rigidity, and loss of smell. Researchers are striving to identify a reliable biomarker for Parkinson's disease. Currently, the Food and Drug Administration has approved the radiotracer I-123-ioflupane injection followed by scanning (DATscan-SPECT) for precise analysis. To diagnose Parkinson's disease early, researchers are developing predictive diagnostic techniques using various biomarkers. The right biosensor can recommend the best personalized course of action to slow the progression of Parkinson's disease. This review highlights the strong performance of diagnostic biomarkers for Parkinson's disease and emphasizes the effectiveness of the common immuno-, apta- and DNA-sensors for their efficient implementations for different biomarkers. Further, it also discusses the potential advantages and drawbacks associated with detection methods for improving high-performance diagnostics.

    • Modern Approaches to Diabetes: The Role of Phytochemicals in Targeting Molecular Receptors

      https://doi.org/10.2174/0115680266352449250612211106
      Introduction

      Diabetes mellitus (DM) is a chronic metabolic disorder characterized by the impaired utilization of glucose, insulin resistance, or reduced insulin production. Although conventional pharmacologic agents like metformin, sulfonylureas, and thiazolidinediones are effective in regulating elevated blood glucose levels, they are often associated with some adverse effects, such as weight gain and liver problems.

      The present review summarizes the possibility of using phytochemicals as safer alternatives for the management of DM by modulation of molecular receptors.

      Methods

      Several studies have reported that certain antioxidant phytochemicals exhibit inhibitory effects on key signaling pathways involved in glucose metabolism and insulin sensitivity under conditions. Therefore, this review will focus on the therapeutic potential of phytochemicals in modulating molecular targets, such as PPARs, GPR119, free fatty acid (FFA) receptors, glucocorticoid receptors, and others. For this purpose, a systematic and extensive literature search was carried out to obtain relevant data, focusing on the prospect of phytochemicals in modulating molecular receptors for diabetes mellitus (DM) management. Electronic databases, including PubMed, Scopus, ScienceDirect, and Google Scholar, were accessed for articles up to March 2025.

      Results

      Curcumin, resveratrol, and quercetin are bioactive molecules that increase the sensitivity of the body to insulin and protect the pancreatic β-cells from oxidative stress. Natural agents, such as garlic, green tea, and blackcurrants, possess an antidiabetic action by inhibiting enzymes, such as α-glucosidase, and increasing the uptake of glucose. The co-administration of synthetic drugs along with natural agents has a synergistic effect in improving glycemic control with fewer side effects. Examples include resveratrol with metformin or curcumin with thiazolidinediones.

      Conclusion

      The findings of this review should be validated at the clinical level in future research studies, including toxicity profiling and formulation optimization, to maximize the therapeutic potential of phytochemicals in the management of DM.

    • Microalgae and Human Disorders: Mechanistic Insights and Therapeutic Potential

      https://doi.org/10.2174/0115680266365289250701180840

      Microalgae, which are primarily autotrophic organisms, have caught the spotlight due to their impressive growth rates and broad distribution. They’re particularly exciting because of their biocompatibility and the wide range of biological activities they offer. Species like and exhibit high antioxidant, anti-inflammatory, antimicrobial, anticancer, antihypertensive, anti-lipidemic, and anti-diabetic properties, making them a promising element in therapeutics. This review discusses the bioactive compounds present in microalgae, including peptides, polysaccharides, and lipids, and their mechanisms of action in disease diagnosis and prognosis. In addition, emerging reports on the synergistic effects of microalgae bioactive compounds in enhancing immune and gut health are discussed. Despite this, challenges in the extraction, cultivation, and commercialization of microalgae-based bioactive compounds remain significant hurdles for a great extent of application. This review examines the challenges and proposes relevant approaches to improve bioavailability and to optimize the cultivation of microalgae. The review underscores the significance of microalgae-derived bioactive agents for pharmaceutical and biomedical applications.

    • Exosome-Mediated Strategies for Melanoma Eradication: A Comprehensive Review

      https://doi.org/10.2174/0115680266373170250624095758
      Introduction

      Exosomes, which are vesicles that are naturally derived and contain a biomolecular payload, are promising vehicles for melanoma therapy because of their biocompatibility, targeting capabilities, and stability. This review emphasizes their capacity to circumvent the constraints of conventional treatments.

      Methods

      We carried out a comprehensive search of PubMed, ScienceDirect, and Google Scholar for peer-reviewed articles published between 2015 and 2024 utilizing terms such as “exosomes,” “melanoma,” and “chemotherapy.” Studies on exosome characterization or non-melanoma malignancies were excluded from the inclusion criteria, which centered on exosome-based therapeutics.

      Results

      Drugs delivered exosomes, such as small interfering RNA (siRNA) and chemotherapeutics, demonstrated enhanced tumor accumulation, achieving 2.5 times greater bioavailability and resulting in a tumor reduction of 60 to 90% when compared to their free counterparts. Surface modifications, such as cRGD peptides, have been shown to enhance targeting capabilities, whereas exosome-mediated photodynamic therapy has been effective in augmenting reactive oxygen species generation and promoting apoptosis.

      Discussion

      Exosomes tackle significant challenges such as drug resistance and systemic toxicity; however, they encounter obstacles related to scalability and immunogenicity. Their dual function in tumor advancement and treatment highlights the necessity for standardized protocols.

      Conclusion

      Exosome-based therapies signify a groundbreaking advancement in the treatment of melanoma. Future endeavors should refine engineering methodologies, enhance production capabilities, and substantiate effectiveness through rigorous clinical trials.

    • Advances in the Directed Evolution of Computer-aided Enzymes

      https://doi.org/10.2174/0115680266377310250526045137

      Experimental-driven directed evolution has achieved remarkable success in enzyme engineering. However, it relies on random mutagenesis and high-throughput screening, both of which have certain limitations, particularly the randomness of mutagenesis and the extensive screening workload that slows down the method's rapid development. In contrast, computer-aided directed evolution combines computational simulations with experimental techniques, providing an efficient and precise approach to enzyme rational design and optimization. By integrating computational tools, researchers can streamline the enzyme design process, improving the accuracy of mutations and screenings, which in turn accelerates enzyme optimization. This review comprehensively introduces the commonly used methods and applications of computer-aided directed evolution, discussing the tools and techniques frequently used in protein sequence analysis and structural analysis. It also covers computational simulation and prediction strategies such as homology modeling, molecular docking, molecular dynamics simulations, machine learning algorithms, and virtual screening. These tools play a critical role in predicting the effects of mutations on enzyme function and optimizing enzyme performance. Moreover, the review explores widely adopted semi-rational and rational design strategies in enzyme engineering, which combine computational predictions with experimental validation to effectively improve enzyme performance. Additionally, the article delves into the challenges and bottlenecks encountered in applying computational technologies in directed evolution, including issues related to computational precision, data quality, and the complexity of enzyme-substrate interactions. Despite these challenges, the future of computer-aided directed evolution holds great promise, with advancements in computational power, machine learning, and multi-omics data integration offering tremendous potential to overcome current limitations.

      In conclusion, this review aims to provide valuable insights for researchers in enzyme engineering, assisting them in developing new, efficient enzymes by integrating both experimental and computational approaches.

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