Mini Reviews in Medicinal Chemistry - Online First

Polysaccharide-based iron oxide nanoparticles, particularly PSC-iron oxide nanoparticles, have emerged as promising agents for brain cancer diagnosis and therapy. Originally approved for anemia treatment, PSC-iron oxide nanoparticles leverage extended circulation time, biocompatibility, and MRI contrast capabilities to serve dual diagnostic and therapeutic roles. This review highlights its application in brain tumor management, focusing on enhanced MRI visualization of tumor vascularization and macrophage activity compared to gadolinium-based agents, which improve tumor delineation and treatment monitoring. Additionally, PSC-iron oxide nanoparticles exhibit immune-modulating properties that promote anti-tumor macrophage responses. Preclinical evidence supports the synergistic effects of this approach with existing therapies and its potential in hyperthermia applications. Challenges in clinical translation, including dosage optimization and safety, require further investigation. This review highlights the potential of PSC-iron oxide nanoparticles in current findings to advance precision medicine or nanomedicine approaches for brain tumors.

Psoriasis is a chronic inflammatory skin disorder affecting 2-3% of the global population. It is increasingly recognized for its systemic comorbidities, especially cardiovascular diseases (CVDs). Notably, severe psoriasis independently increases cardiovascular disease (CVD) risk. This elevation occurs beyond conventional risk factors, such as hypertension and diabetes. It suggests that shared inflammatory pathways underlie the association between severe psoriasis and atherosclerotic conditions, like coronary artery disease (CAD). Atherosclerosis, characterized by lipid-laden plaque formation in arterial walls, remains a leading contributor to CVD-related morbidity and mortality. Emerging evidence underscores the interplay of inflammatory cell heterogeneity and immune dysregulation in its pathogenesis, mirroring mechanisms observed in psoriasis. The overlapping systemic inflammation and immune dysfunction in both diseases suggest potential therapeutic synergies. CD4⁺ regulatory T cells (Tregs), pivotal immunosuppressive modulators, have shown promise in mitigating autoimmune responses, yet their therapeutic exploitation in psoriasis-atherosclerosis comorbidity remains underexplored. This review summarizes current insights into Tregs' roles in psoriasis and atherosclerosis, emphasizing their dual regulatory functions; in psoriasis, Treg dysfunction exacerbates interleukin-17 (IL-17)/23-driven keratinocyte hyperproliferation, while in atherosclerosis, impaired Treg activity permits pro-inflammatory cytokine cascades and foam cell formation. We, herein, highlight emerging approaches to enhance Treg stability and function, such as nanotechnology-based targeting antibodies and traditional Chinese medicine (TCM). By delineating Treg-centric mechanisms across both diseases, this review proposes a paradigm shift toward immunomodulatory therapies addressing psoriasis-atherosclerosis crosstalk, offering novel strategies to alleviate systemic inflammation and cardiovascular burden in psoriatic patients. Further research into Treg heterogeneity and microenvironmental cues may unlock precision therapies for this comorbid axis.

As the main fermentation product of Aspergillus fumigatus (A. fumigatus), fumagillin is directly related to the gene of A. fumigatus and exhibits a variety of biological activities. However, its clinical application is limited by low yield and toxicity. It is of great significance to improve the yield and safety of fumagillin using A. fumigatus. Currently, research on fumagillin at home and abroad primarily focuses on a single direction and lacks a systematic review of its biosynthesis, structure-activity relationship, and strain modification technology, as well as a comprehensive theoretical framework. This study systematically reviews the biosynthesis mechanism, activity characteristics, and targeted strain modification technology of fumagillin, providing theoretical support for breakthroughs in production, toxicity regulation, and clinical transformation of fumagillin.

The primary feature of Parkinson's disease (PD), a progressive neurodegenerative disease that results in both motor and non-motor dysfunctions, is the degeneration of dopaminergic neurons in the substantia nigra. In recent years, indole-based compounds have emerged as promising candidates for developing novel treatments for Parkinson's disease due to their diverse pharmacological properties. Among the significant pathogenic targets against which indole derivatives exhibit potent activity are monoamine oxidase (MAO), NMDA receptors, oxidative stress, and neuroinflammation. This review provides an in-depth analysis of synthetic indole derivatives as potential therapeutic agents for Parkinson’s disease. We explore how these compounds may reduce the pathology associated with Parkinson's disease, identify molecular targets, and analyze the relationships between their structure and activity. We also discuss recent advances in computational and medicinal chemistry that aim to enhance indole structures. Potential challenges and upcoming prospects for the therapeutic application of indole-based therapies are also considered in the review. The ultimate objective of this study is to elucidate the potential applications of synthetic indole derivatives in the development of innovative therapies for Parkinson's disease.

Glucose control remains the primary target in the treatment of both Type 1 and Type 2 diabetes. Glycemia plays a major role in preventing both macrovascular and microvascular complications. Some diabetes medications can also affect body weight. This article describes the various categories of antidiabetic medications and their effects on weight and HbA1c (Hemoglobin A1c) levels in patients with Type 1 and Type 2 diabetes. The weight and glycemic control effects of antidiabetic drugs approved for the management of weight loss are also reviewed in this article. Several types of medications are available that work through different mechanisms to help lower blood glucose levels. The risk of weight gain or weight loss depends on both the medication used and lifestyle factors such as diet and exercise. A reduction in glycosuria is the primary reason for weight gain; however, reducing calorie intake can help minimize this effect. Nevertheless, due to limited access to adequate nutrition education, many people are unable to complement changes in medical therapy with necessary lifestyle adjustments. Some diabetes medications can cause weight loss by getting rid of extra glucose from the body or lowering the amount of glucose our liver makes. Some diabetes medications have little to no effect on weight for most people, and healthcare professionals sometimes refer to these as “weight-neutral” diabetes medications. Certain medications promote weight loss in addition to exerting extra-glycemic and extra-pancreatic effects, which positively impact cardiovascular risk by reducing both mortality and morbidity. Verification and further explanation of the actual mechanisms underlying the life-prolonging effects of these antidiabetic medications are still needed. Their effects on biomarkers that mimic calorie restriction in patients also require confirmation. Additional research should be conducted to clarify the details of lifespan extension. Furthermore, when herbs are administered alongside antidiabetic medicines, they may alter the pharmacokinetic and pharmacodynamic properties of the drugs, rendering them less effective or potentiating their activity and producing adverse effects.

The mounting threat of antimicrobial resistance has intensified the global search for novel antibacterial agents, and chalcones - the aromatic ketones characterized by an α, β-unsaturated carbonyl system has emerged as promising scaffolds against the threat of antimicrobial resistance. This review presents a detailed exploration of chalcones as potent antibacterial agents, emphasizing their structural versatility, mechanisms of action, and therapeutic potential. With a modular backbone that supports diverse substitutions and heterocyclic extensions, chalcones can be easily synthesized and chemically optimized to target a broad spectrum of bacterial pathogens, including multidrug-resistant strains such as MRSA and VRE. Mechanistically, chalcones exert antibacterial effects through multiple pathways, like disrupting bacterial membranes, inhibiting cell wall biosynthesis, interfering with DNA replication via DNA gyrase and topoisomerase IV, and suppressing protein synthesis. Their amphipathic nature and ability to bind critical bacterial enzymes offer an advantage in circumventing classical resistance mechanisms. Structure-activity relationships and computational studies have further elucidated the influence of electron-donating and electron-withdrawing groups, positional isomerism, and heterocyclic integration on antibacterial potency. A review of recent literature underlines the efficacy of chalcone derivatives against Gram-positive and Gram-negative strains, with many compounds demonstrating promising activity, such as compound 85 with MIC 3.4 nM against Ciprofloxacin with MIC 4.7 nM. The review also highlights advancements in green synthesis, QSAR modeling, and molecular docking, which collectively facilitate the rational design of next-generation chalcone-based antibacterials. Altogether, chalcones represent a structurally simple yet biologically robust class of compounds, offering significant promise as adaptable and effective agents in the evolving landscape of antimicrobial therapy.

Ruthenium complexes stand out as an excellent alternative in the field of organometallic chemistry with applications in various areas. Recently, in cardiovascular pharmacology, there has been a growing interest in investigating complexes that modulate the Nitric Oxide (NO) pathway without necessarily and directly donating NO. NO has a proven vasodilatory and cardioprotective effect, and it is known that reduced levels are associated with an increased risk of CardioVascular Diseases (CVD). Studies suggest that ruthenium complexes significantly contribute to the treatment of CVD pathophysiology through different pharmacological mechanisms, including the precise delivery of carbon monoxide (CO) to the molecular target, the release of nitric oxide species under visible and invisible (UV) light, the ability to stimulate the activation of soluble Guanylate Cyclase (sGC) enzyme, participation in the opening of potassium channels, and reduction of cytoplasmic calcium levels. This study aims to conduct a narrative review of the cardiovascular effects of ruthenium complexes, focusing on hypertension and myocardial injury, and demonstrate that metal complexes acting on the NO pathway may have promising targets for the development of therapeutic strategies in CVD treatment.

Cardiovascular diseases are the leading cause of death worldwide. Despite the development of a wide variety of drugs, treatment regimens do not seem to be able to prevent the progression of these pathologies. In recent years, the study of epigenetic mechanisms has led to the discovery of new targets that may facilitate the search for therapeutic alternatives. Furthermore, it has been demonstrated that the onset of cardiovascular diseases is associated with changes in DNA methylation status and altered histone modification patterns. Therefore, the use of natural and synthetic inhibitors of epigenetic modulators, such as DNA methyltransferases (DNMTs), is likely to constitute a new approach in the therapy of cardiovascular diseases. In this review article, we discuss the mechanisms of action of inhibitors of epigenetic modulators and their applications in the treatment of cardiovascular diseases.