Mini reviews in medicinal chemistry最新文献

Acorus calamus, a perennial herbaceous plant with a long history of traditional use, is attracting scientific interest for its diverse bioactive compounds and therapeutic potential. This review investigates its medicinal properties, including neuroprotection, anti-inflammatory effects, and antihyperglycemic activities, primarily attributed to compounds such as α-asarone. A. calamus also has antimicrobial activity against bacteria and fungi, making it a natural antibiotic. Its antioxidative and cardioprotective properties are promising for cardiovascular health, while its antispasmodic and neuroprotective properties suggest applications in neuromuscular and cognitive disorders. Ongoing research aims to decipher mechanisms, dosing, and safety, bridging traditional practices with modern healthcare options.

Marine organisms produce a diverse array of secondary metabolites with significant pharmacological potential, particularly in the development of anti-cancer, anti-microbial, antifungal, and anti-viral therapies. Despite challenges in isolation and cultivation, marine-derived compounds, such as Didemnin B, Psammaplin A, and Dolastatin, have shown promise in cancer treatment, while other metabolites exhibit potent activity against drug-resistant bacteria, fungi, and viruses. These compounds have excellent potential for treating various infections, for example, MRSA (eicosapentaenoic acid and fridamycin), Candida albicans (aurantoside K), and HIV-1 and HIV-2 (sulfoquinovosyl diacylglycerol). These unique compounds offer new avenues in drug discovery, addressing current limitations in traditional therapies. This review provides an overview of the pharmacological potential of marine organisms, focusing on their applications in overcoming drug resistance and developing novel treatments for cancer, infections, and viral diseases. Sustainable approaches for harvesting these compounds are essential for future research.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the formation of senile plaques and neurofibrillary fiber tangles. Studies have shown that increased regional iron loading in the brain, dysregulation of iron homeostasis in the body, oxidative stress, and protein and lipid oxidation are all involved in the pathogenesis of AD. Ferroptosis, an irondependent, lipid peroxidation-driven form of regulated cell death, is increasingly implicated in the pathological process of AD, and some new compounds targeting ferroptosis demonstrate therapeutic efficacy in both cellular and animal models of AD. Therefore, this article systematically summarizes recent advances in the role of ferroptosis in AD pathogenesis and highlights progress in targeting ferroptosis for AD treatment, providing insights for future therapeutic and preventive strategies.

Cancer continues to pose a worldwide health concern, requiring breakthrough therapeutic approaches that are both efficacious and minimally intrusive. Berberine, a natural isoquinoline alkaloid, has attracted considerable interest due to its various pharmacological features, particularly its strong anticancer effects. Nonetheless, its clinical application has been impeded by inadequate bioavailability, rapid metabolism, and systemic elimination. Recent breakthroughs in nanotechnology have mitigated these issues by creating BBR nanoparticles (BBR NPs), which provide increased solubility, precise delivery, and higher therapeutic efficacy. This paper extensively examines BBR and its nanoparticle forms for cancer treatment. The mechanisms of action, including apoptosis induction, tumour angiogenesis inhibition, antimetastatic effects, and oxidative stress modulation, are thoroughly examined. Essential synthesis approaches for BBR nanoparticles, including chemical reduction, green synthesis, and encapsulation in nanocarriers, are discussed together with their characterization methodologies. The report emphasizes comparative studies that illustrate the enhanced antitumor efficacy of BBR nanoparticles compared to free BBR in preclinical settings. Notwithstanding encouraging results, nanoparticle stability, scalability, and regulatory obstacles must be resolved for effective clinical translation. Future directions are examined, encompassing advancements in nanoparticle design and their prospective incorporation into personalized oncology. This review highlights the transforming potential of BBR and its nanoformulations as a novel therapeutic approach in cancer treatment.

Since its discovery in 1979, the tumor suppressor p53 has been widely studied and expressed in various organisms, including yeast. Yeast has proven to be a very informative model and an effective system for studying the roles and functions of this protein and gene. This review is a compilation of our team's studies involving p53 expression in yeast. These researches investigated certain aspects, essentially the apoptotic function of p53. Our main contribution to the study and understanding of the p53 gene in the yeast context is the confirmation of a negative effect of p53 on cell growth in both Saccharomyces cerevisiae and Pichia pastoris strains, which ultimately led to apoptotic cell death. This involves a high dose of p53 and the NLS signal, which enables p53 to target both the mitochondria and the nucleus. Prior to that, obtaining the whole protein required a cDNA without its UTR. Thus, a yeast model was developed, allowing verification of p53 activity. Cancer mutants and their revertants could thereby be assessed. This has evolved into a real antioxidant/anti-apoptotic molecular screening mechanism. Two primary applications were achieved: testing the co-expression with the thioredoxin 2 gene (TRX2) and assessing the impact of Nigella sativa seed extracts. Furthermore, the high yield of yeast P53 production allowed its use in serological cancer diagnosis.

The method of discovering new drugs is costly, time-consuming, laborious, and associated with a high failure rate. Various techniques have been applied in modern drug discovery to resolve these issues and discover novel pharmacologically active agents. Natural products are one of the sources of drugs that have long been used to treat various illnesses. Kojic acid (KA) is a naturally produced bioactive chemical with a 3-hydroxy-4-pyranone skeleton made by numerous aerobic microbes, such as Aspergillus and Penicillium. KA is a potent tyrosinase inhibitor used in cosmetics to lighten skin by reducing hyperpigmentation. In this review, beyond its cosmetic applications, it exhibits versatile biological activities, including anticancer, antibacterial, antifungal, antioxidant, antiviral, anti-inflammatory, anticonvulsant, anti-Alzheimer's disease, antidiabetic, and metalchelating properties. KA and its analogs have been reported as promising radioprotective agents capable of mitigating the harmful effects of ionizing radiation. By integrating KA with pharmacologically active scaffolds, researchers have developed potent hybrids, such as aminochloroquinoline- KA derivatives, which demonstrate vigorous β-hematin inhibitory activity and significant efficacy against both delicate and resilient strains of P. falciparum to chloroquine. The approach taken to prepare this review article involved collecting, assessing, and synthesizing relevant literature from different databases. This review systematically explores the comprehensive therapeutic potential of KA and its derivatives, including Mannich base, thiazoles, and 1,2,3-triazoles, for various activities, with Michael Adducts and dinuclear ruthenium complexes which exhibits promising antitumor activity. Combining current knowledge will provide a comprehensive foundation for the rational design and development of clinically relevant agents based on KA pharmacophores.

Introduction: This review explores the complex relationship between Iron Deficiency Anaemia (IDA) and glycated haemoglobin (HbA1c) levels, a critical marker for diabetes mellitus. The objective is to evaluate how IDA influences HbA1c measurements and its implications for diabetes diagnosis and management, particularly in populations with high IDA prevalence.

Methods: A narrative mini-review was conducted, synthesizing evidence from studies identified through PubMed, MEDLINE, and Google Scholar. The search focused on English-language articles published between 1982 and 2024, adhering to PRISMA guidelines. Studies were selected based on their relevance to IDA and HbA1c, with 57 articles meeting the inclusion criteria after rigorous screening.

Results: The review revealed conflicting findings: some studies reported elevated HbA1c levels in IDA patients independent of glycemic status, potentially leading to diabetes overdiagnosis, while others found no significant association. Proposed mechanisms included altered erythrocyte turnover, structural haemoglobin modifications, and oxidative stress-induced glycation. Iron replacement therapy was shown to normalize HbA1c levels in many cases, underscoring the importance of addressing iron status in diabetic patients with concomitant anaemia.

Discussion: The findings highlight the need for cautious interpretation of HbA1c results in IDA patients, especially in high-risk groups like premenopausal women. Alternative glycemic markers, such as glycated albumin or fructosamine, may be valuable in such scenarios. Methodological variations in HbA1c measurement and population differences were identified as key confounding factors.

Conclusion: The study underscores the intricate interplay between IDA and HbA1c, emphasizing the necessity of considering iron status in diabetes diagnosis and management. Future research should focus on standardizing assessment protocols and elucidating the molecular pathways linking iron metabolism to haemoglobin glycation. These insights are crucial for improving diagnostic accuracy and therapeutic outcomes in affected populations.

The drug discovery process is highly intricate and complex. Driven by unprecedented advances in AI technology, the application of artificial intelligence in drug discovery (AIDD) is showing significant growth, and AIDD has the potential to fundamentally change and revolutionize traditional drug development models in the foreseeable future. We selected 7061 literature studies on artificial intelligence used in drug discovery from the Web of Science Core Collection database from 2000 to 2024, and adopted bibliometric tools, such as Citespace, VOSviewer, and RStudio, to select nodes for knowledge graph generation and visualization analysis by using country, institution, author, and keywords. The results showed that from 2017 to 2024, the literature on the use of artificial intelligence for drug discovery exploded, with the United States having the largest number of papers, and China's number of papers growing rapidly and surpassing the United States in the last two years. Molecular docking, virtual screening, algorithm optimization, interpretable AIDD, protein language modeling, drug targets, and protein interaction prediction were found to be the research hotspots in this field in recent years. AI has been widely used in the field of drug research and development. Based on the quantitative analysis of the literature on the use of artificial intelligence in drug discovery, this paper has revealed the current research status in this field, clarified the current research hotspots and future research trends, and provided certain references for researchers to plan future research directions.

In the ongoing battle between the immune system and cancer, a unique subset of T cells has quietly emerged as a key player. Tissue-Resident Memory T (TRM) cells, strategically positioned within tissues, are redefining our understanding of localized immune defense and tumor control. This review aims to bridge this knowledge gap by synthesizing current concepts of T cell immune surveillance with foundational aspects of TRM cell biology. We explored clinical evidence supporting the prognostic and therapeutic relevance of TRM cells in various cancer contexts, including their emerging roles in enhancing responses to immunotherapy. Furthermore, we discussed innovative strategies that exploit TRM-phenotype cells for patient stratification, disease staging, and therapeutic development. Key challenges such as the absence of standardized T cell nomenclature and the limited understanding of how TRM markers relate to tumor biology are critically examined. By integrating basic science and clinical observations, this review provides a comprehensive overview of the field and highlights promising avenues for future research to harness TRM cells in precision oncology.

There is an urgent need to develop effective antiviral treatments against SARS-CoV-2. Despite the availability of vaccines, drug discovery remains critical for combating emerging variants. Molecular docking studies have become a vital computational tool for identifying antiviral drugs capable of inhibiting different SARS-CoV-2 proteins. This review explores the role of metal complexes as promising viral inhibitors through in silico molecular docking approaches. The binding abilities of several coordination complexes derived from iron, copper, palladium, and zinc ions have been evaluated against major viral proteins such as the spike glycoprotein, RNA-dependent RNA polymerase (RdRp), and the main protease (Mpro), which are responsible for viral infection. Comparative docking studies of specific metal-based compounds with conventional antiviral drugs highlight their superior binding affinities and inhibitory potential. Furthermore, ADME (Absorption, Distribution, Metabolism, and Excretion) analyses, molecular dynamics simulations, and drugdelivery strategies are discussed to assess pharmacokinetics and therapeutic viability. Overall, this review emphasizes the importance of molecular docking in the rational design of metal complexes as antiviral agents and its relevance for developing effective therapeutic strategies to combat COVID-19.