Mini Reviews in Medicinal Chemistry - Online First

The increasing rise of multidrug-resistant bacteria necessitates an urgent need for the discovery of novel antibacterial agents. Natural products have long been a source for identifying and isolating novel antibacterial agents. Anacardic acids (AAs), a phenolic lipid isolated from solvent-extracted cashew nutshell liquid (CNSL) of Anacardium occidentale (Family Anacardiaceae), have garnered potential attention for their potent antibacterial properties. Besides Anacardium occidentale, different analogues of AAs have also been isolated from various natural sources. These natural and structurally optimized derivatives exhibited potential antibacterial properties against other bacterial strains. Although AAs are associated with a high level of antimicrobial activity against P. acnes, S. mutans, S. pyogenes, H. pylori, and methicillin-resistant S. aureus, their poor physicochemical properties are a major concern for their clinical translation. Encapsulating AAs in nanoformulations could be beneficial, as it can improve their poor pharmacokinetic properties, prevent enzymatic degradation during transport in the body, and facilitate site-specific release, thereby enhancing their therapeutic potential. Among the different nanocarriers studied, zein nanoparticles loaded with anacardic acid showed strong antibiofilm activity against E. faecalis, S. aureus, and P. aeruginosa.

In contrast, the DNase-chitosan-coated solid lipid nanoparticles (Ana-SLNs-CH-DNase) demonstrated superior activity in disrupting mature S. aureus biofilms. Additionally, we have discussed the structure-activity relationship and mechanism of action of AAs, where it was found that AAs disrupt cell membrane functioning, inhibit bacterial respiration, quorum sensing, and cellular respiration, among other effects. These findings suggest that AAs and their analogues exhibit promising antibacterial activity, while nanoformulations offer a promising strategy to optimize their therapeutic potential.

Parkinson’s Disease (PD) is a neurological disease marked by the buildup of α-synuclein. The main symptom of the disease is the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc). Gene therapy may be a treatment option for PD and has been used in clinical trials to treat a variety of illnesses in the human brain. Currently, the majority of gene therapy clinical studies are being conducted to treat PD. The primary objective is to enhance medications that address motor issues. Patients with PD have been the subjects of several gene therapy treatment techniques that have been developed and tested. Genes are typically transported to neurons in brain regions relevant to PD, such as the striatum, using viral vectors. It may only be necessary to administer these gene delivery methods once, and they may induce expression to persist for an extended time. Several neurotrophic factors, including neurturin, GDNF, BDNF, CDNF, and VEGF-A, have demonstrated promising outcomes in preclinical models as potential disease-modifying targets that may slow disease development. Currently available treatment regimens for PD mostly comprise the administration of levodopa (L-DOPA), dopamine agonists or MAO-B inhibitors, or surgery in the form of deep brain stimulation or neuroablative surgery, among other options. Many different targeting moieties for PD treatment, as well as current treatment techniques and gene therapy methodologies, are covered in this review article. The research reviewed the relevant literature on the potential role of gene therapy for the treatment of PD. The research articles are obtained through various databases, including ScienceDirect, Scopus, PubMed, and Google Scholar. This review includes various targeting moieties for the treatment of PD, current PD treatment strategies, PD treatment using gene therapy, comparison of risk-benefit ratios of gene therapy vs. DBS/drugs, and gene vector technology in the treatment of PD. This review compiles data on Parkinson's disease, its current treatment strategies, and the potential role of gene therapy in its treatment.

Phenothiazine and its N-substituted derivatives are pivotal in heterocyclic chemistry, and serves as potential building blocks in chemical and pharmaceutical sciences. Over the past decade, extensive research has focused on the medicinal potentials of these compounds, exploring their anticancer, analgesic, anti-tumor, anti-inflammatory, and antibacterial properties. Due to their distinctive chemical compositions, phenothiazine and its N-substituted derivatives have facilitated the development of novel substitutions. This paper reviews recent advancements in the synthesis of phenothiazine and its N-substituted derivatives, with an emphasis on their potential biological roles. Numerous investigations have identified various types of phenothiazine and its N-substituted derivatives that exhibit compelling biological characteristics. It discusses the impact of different functional groups on phenothiazine at the N-substitution, specifically Cl, CF3, OH, N(C2H5)2, and (CH2)5CH3. Furthermore, the relationship between the biological activities and the structural characteristics of the compounds is examined, identifying the chemical groups and structural alterations that enhance bioactivity, reduce toxicity, and improve handling.

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.

Inflammation is the body's defensive response to injury, infection, or external stimuli. While NSAIDs and corticosteroids are widely used to treat inflammatory diseases, their long-term application often leads to severe side effects, including gastrointestinal damage and cardiovascular toxicity, as well as drug resistance. This underscores the urgent need for developing safer and more effective anti-inflammatory agents. Natural products, particularly terpenoids, as the largest class of bioactive compounds, have garnered significant attention due to their potent anti-inflammatory properties and structural diversity. Through systematic structural modifications, researchers have developed numerous terpenoid derivatives with enhanced anti-inflammatory efficacy, providing valuable insights for drug discovery. This review comprehensively summarizes the anti-inflammatory mechanisms and therapeutic potential of terpenoids and their derivatives over the past decade, offering new perspectives for anti-inflammatory drug development and identifying promising candidates for further investigation.

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.