Mini reviews in medicinal chemistry最新文献

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 antiinflammatory 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.

Imidazo[2,1-b][1,3,4]thiadiazoles, a class of fused bicyclic heterocycles, have garnered significant interest in medicinal chemistry due to their diverse biological activities, particularly their anticancer properties. Over recent decades, extensive research has been conducted to explore and enhance their therapeutic potential. This comprehensive review spans six decades of research on the imidazo[2,1-b][1,3,4]thiadiazole scaffold, focusing on structural variations at C-2, C-5, and C-6 position on this scaffold and their implications for anticancer activity. Modifications at these positions have been shown to significantly impact the compound's efficacy against various cancer cell lines. Continuous exploration and optimization of these substitutions hold promise for the development of novel anticancer therapeutics.

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.

Chronic Obstructive Pulmonary Disease (COPD) is a respiratory condition defined by persistent bronchitis, emphysema, and structural remodelling. The number of cases has risen globally; however, limited viable remedies exist. It is linked to airway blockage, oxidative stress, chronic conditions, inflammation, excessive mucus production, and increased autophagy and cellular senescence. Beta-2 adrenergic receptors (β2-ARs) play a significant role in both the aetiology and management of COPD. Beta-2 agonists (particularly long-acting beta-agonists, or LABAs) are preferable in COPD therapy due to their powerful bronchodilation, rapid onset, prolonged duration, and potential synergistic effects with other medications. They are well-tolerated and effective in improving the quality of life and reducing exacerbations, making them an essential component of COPD treatment. Currently, there are fewer bronchodilators that have been found to be effective. This leads to an exploration of novel, long-acting, and ultra-long-acting drugs for the management of COPD. This article provides an extensive overview of natural β2 agonists. The current study emphasizes the rational development of lead candidates, including trantinterol, isopropyl, tert-butyl, and heterocyclic ring 2-amino-2-phenylethanol derivatives, 8-(2-amino-1-hydroxyethyl)-6-hydroxy-1,4- benzoxazine-3(4H)-one derivatives (non-substituted, methyl-substituted, dimethyl-substituted), 5- (2-amino-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one analogues, indacaterol analogues, saligenin antedrugs, and saligenin alkoxyalkylphenyl sulfonamide derivatives, accompanied by molecular docking studies.This paper also highlights numerous structure-activity relationship investigations and various novel β2 agonists currently in clinical trials and patents. The present review will significantly aid in fostering the research of COPD.

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.

Three-dimensional (3D) printing is a transformative technology that has significantly influenced multiple sectors, including aviation, defence, architecture, and, more recently, healthcare and pharmaceuticals. Despite its growing adoption, there remain gaps in consolidated knowledge regarding its material versatility, regulatory considerations, and real-world implementation in clinical and pharmaceutical settings. Challenges related to biocompatibility, scalability, and the standardization of printed products hinder its full integration into medical practice. Addressing these issues requires a comprehensive understanding of the technological foundation, materials, and evolving applications of 3D printing in medicine. This review aims to provide an in-depth analysis of current advances, limitations, and prospects of 3D printing in healthcare. A systematic literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar databases, focusing on peer-reviewed articles published between 2010 and 2024. The review highlights key fabrication techniques, material innovations, clinical applications, and integration with emerging technologies, addressing critical challenges and opportunities for advancing personalized medicine.

Introduction: Isatin (1H-indole-2,3-dione) and indole are versatile scaffolds with diverse pharmacological activities, including antimicrobial, anticancer, antiviral, anticonvulsant, antiinflammatory, and analgesic effects. Isatin-indole hybrids have emerged as multifunctional agents with significant potential in drug discovery.

Methods: A literature survey (2010-2025) across major databases (PubMed, Google Scholar, ACS, etc.) included reports on synthesis, biological evaluation, and structure-activity relationship (SAR) analysis.

Results: Numerous synthetic approaches, including both conventional and green methods, have yielded a diverse range of isatin-indole derivatives. Many exhibited potent antimicrobial, anticancer, antioxidant, and antitubercular activities, with SAR studies highlighting the impact of substitution patterns on activity and selectivity.

Discussion: This review aims to provide a comprehensive overview of hybrid molecules in which the isatin core is covalently linked to an indole scaffold. It focuses on their synthesis, diverse biological activities and structure-activity relationship (SAR) studies from 2001 onwards.

Conclusion: This review provides a concise summary of the latest developments and future outlook for the therapeutic potential of isatin-indole hybrids in the development of potent bioactive drugs.

Inflammatory Bowel Disease (IBD), which includes ulcerative colitis and Crohn's disease, accounts for chronic inflammation in the entire gastrointestinal tract. Conventional treatments, such as amino salicylates, corticosteroids, immunomodulators, and biologics, can all alleviate symptoms; however, they may cause unwanted side effects and are extremely expensive. Most of the time, long-term treatment is also less effective. This review aims to discuss natural products (NPs) with therapeutic potential for IBD, emphasizing flavonoids, terpenoids, polysaccharides, and alkaloids. The compounds have been chosen based on literature reporting antiinflammatory, antioxidative, and immunomodulatory activities that relate to IBD pathophysiology. Preclinical evidence using in vivo and in vitro models and available clinical data provides the basis for the main pharmacological effects, mechanisms of action, and safety profiles of these NPs. The key molecular pathways that are targeted include the NF-κB, MAPK, and JAK/STAT signaling pathways, as well as the establishment of the gut microbiota and intestinal barrier functions. Standardization, bioavailability, and maximal dosing remain challenging issues even when experimental models show promising results for various NPs. Hence, this review stresses the urgency for well-designed clinical trials and suitable formulation approaches to translate these observations into efficacious and evidence-based therapies. Being a natural remedy option, NPs could be considered complementary or alternative treatments for IBD, demanding further interrogation within an integrated therapeutic paradigm.

Neurological disorders (NDs) are diseases that arise due to deformities mainly in the central nervous system (CNS) and also affect the nerves throughout the human body. NDs, including Alzheimer's disease (AD), Parkinson's disease (PD), Multiple Sclerosis (MS), and a variety of brain malignancies, pose a major healthcare challenge and are the main cause of mortality on the global scale. There are very limited treatment options for the majority of the NDs, and the currently available drugs commonly fail to penetrate the BBB and deliver the drug to the target effectively. These challenges have necessitated the advent of new drug delivery methods that can cross the BBB with ease and deliver the drug by accurately targeting the diseased area in a safe and biocompatible manner. Nanoparticle-based drug delivery strategies offer significant advantages in BBB penetration and drug delivery due to their unique properties. Carbon dots, among nanoparticles with a size below 10 nm, are highly biocompatible, fluorescent molecules that offer ease of functionalization, drug conjugation, and effective detection within biological systems. The literature is rich in reviews on the synthesis, characterization, and application of CDs. However, a review specifically focused on the therapeutic potential of CDs in major NDs is missing. This review aims to fill that gap by presenting a detailed account of the carbon dot-based therapeutic approaches in the treatment of major NDs. It briefly discusses the properties of CDs, the main routes of synthesis, major raw materials, and key synthesis parameters that affect their properties, while placing a greater emphasis on their therapeutic potential. The review provides a detailed assessment of literature from the past 15 years on the development and current challenges in the application of CDs as therapeutic and drug delivery agents. Our analysis reveals that limited research has been conducted on CD-based therapeutics in NDs, particularly in MS and brain tumors, where original research is scarce. This review article highlights the major developments in the therapeutic uses of carbon dots in NDs, addresses a critical research gap, and provides a comprehensive overview of various studies related to carbon-dot-based therapeutic approaches for major NDs.