Mini reviews in medicinal chemistry最新文献

Introduction: Dendrobium belongs to one of the most important genera of the Orchidaceae family, which covers the largest category of flowering plants. More recent traditional medicinal studies have revealed that these orchid plants are used worldwide to treat a variety of illnesses, including those related to the complexion, pulmonary, gastrointestinal, reproductive, and circulatory systems, as well as cancers, pain, and inflammation. Several Dendrobium species have been the subject of phytochemistry and pharmacological research to explore their different medicinal aspects.

Materials and methods: A comprehensive search through databases (PubMed, Google Scholar, Web of Science, Traditional integrated knowledge resources, local dissertations, and books) was conducted up until November 2024 using key terms such as "Orchid plants, Type 2 diabetes, phytomedicine, natural products, phytoconstituents, phytochemistry, therapeutic potential, and plantderived antidiabetic agents."

Results: Its major phytoconstituents belong to the chemical categories of stilbenoid, glycoside, alkaloids, flavonoids, phenanthrenes, anthocyanins, carotenoids, and bibenzyl derivatives, in which the alkaloids and flavonoids play a most significant role for their biological properties. The flavone Cglycoside and flavanols are commonly found, but highly methylated and glycosylated derivatives of flavonoids are absent in orchid leaves.

Discussion: The phytochemical composition of Dendrobium, along with its structure-activity relationship of major classes, supports it as a potential source for novel antidiabetic agents through integrating traditional knowledge with medicinal chemistry aspects.

Conclusion: A specific Dendrobium orchid plant has a promising role in the effective management of diabetes. In the future, newer, more potent antidiabetic compounds may be isolated and further developed into more effective antidiabetic agents.

Mitochondria, commonly termed the 'cellular powerhouse', produce the majority of cellular adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). In addition to their role in energy synthesis, mitochondria are crucial for maintaining calcium homeostasis, mediating cellular signaling, regulating cell proliferation and apoptosis, and supporting various other physiological processes. In recent years, mitochondria have gained prominence as a critical target for the treatment of metabolic disorders. Research has demonstrated a strong association between mitochondrial dysfunction and the pathogenesis of metabolic diseases, such as insulin resistance, diabetes, metabolic syndrome, cardiovascular diseases, and endocrine tumors. Consequently, understanding the mechanisms of mitochondrial homeostatic imbalance and developing mitochondria-targeted therapeutics hold promise for innovative treatments of metabolic disorder-related diseases. This article seeks to elucidate recent advancements in the understanding of mitochondrial dysfunction's role in metabolic diseases and offers a comprehensive overview of current therapeutic strategies and approaches for addressing this dysfunction.

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.

Individuals diagnosed with inflammatory bowel disease (IBD) face a significantly heightened risk of developing colorectal cancer (CRC), primarily due to persistent intestinal inflammation that fosters neoplastic transformations across the colon. This narrative review delves into the potential of certain fruits, such as black raspberries, Amazonian açaí, apples, grapes, cocoa, Ziziphus jujuba, and Moringa oleifera, in mitigating IBD-induced CRC. Preclinical studies indicate that these fruits possess anti-inflammatory and antioxidant properties that may disrupt carcinogenic pathways. Notably, black raspberries have demonstrated the ability to modulate epigenetic markers by demethylating tumor suppressor genes and inhibiting DNA methyltransferases (DNMT), like DNMT1 and DNMT3B. This epigenetic modulation influences the Wnt signaling pathway, crucial in CRC development, and affects cellular processes, such as proliferation, apoptosis, and angiogenesis. Animal models further support these findings, showing that black raspberries can suppress β- catenin signaling, reduce chronic inflammation, and decrease tumor incidence. This comprehensive analysis underscores the promising role of specific fruits in CRC prevention among IBD patients and highlights the need for further research to translate these findings into clinical applications, potentially benefiting both public health and the nutraceutical industry.

Musculin antisense RNA 1 (MSC-AS1) is a long non-coding RNA (lncRNA) located on human chromosome 8q13.3-q21.11. Emerging evidence shows that MSC-AS1 is either upregulated or downregulated in 16 types of human cancers, and is associated with clinical pathological features and patient prognosis in 12 of these cancers. It is widely believed that the dysregulation of MSCAS1 contributes to tumor cell growth, metastasis, epithelial-mesenchymal transition (EMT) progression, metabolic reprogramming, and drug resistance formation. Mechanistically, MSC-AS1 can act as a competing endogenous RNA (ceRNA) by sponging 14 miRNAs to affect the expression of downstream mRNAs, or it may directly interact with proteins, both of which contribute to the activation of the PI3K/AKT and Wnt/β-catenin signaling pathways. Our review study suggests that MSC-AS1 is a potential cancer biomarker and therapeutic target. In summary, we have explained the research on MSC-AS1 related to cancer treatment, its expression patterns, functional characteristics, and molecular mechanisms in malignant tumors. We have further emphasized its significance in clinical prognosis and therapeutic applications.

Artificial Intelligence (AI) is emerging as a valuable tool in pharmaceutical formulations, including the development of effervescent tablets (ETs). This review highlights how AI techniques are being explored to support ET formulation designs, optimize component ratios, predict disintegration and dissolution behavior, and control reactions through artificial neural networks, support vector machines, and machine learning. These techniques have been applied in recent studies to enhance stability, improve disintegration times, and flavor masking. Computational fluid dynamics simulations of effervescence and dissolution are underexplored for ETs. Data-driven approaches, like response surface modeling, require ingredient concentrations, tablet properties, consumer preferences, and predictive analytics for optimization. However, limited comprehensive datasets, complex reactions, environmental sensitivities, and ethical/regulatory considerations pose challenges. Overcoming these obstacles, as identified in the current literature, could enable AI to innovate ET development and personalization.

Quinoline is a biologically important bicyclic scaffold found in many natural products and medicinally relevant molecules. Quinoline-containing compounds continue to feature prominently in recent literature on hit identification and hit-to-lead campaigns targeting various biological pathways, underscoring the need for a review of the latest progress. This review presents recently reported quinoline-containing natural products, various synthetic methods for producing quinoline derivatives, and an overview of their diverse biological activities. The biological properties covered include anticancer, anti-inflammatory, antioxidant, anti-tubercular, α-glucosidase inhibitory, antimicrobial, anti-Alzheimer's, and antimalarial effects. Finally, a selection of representative quinolinebased chemical probes is presented to assist researchers in strategically designing novel quinoline derivatives for diverse biological applications.

Recent trends have shown the development of various medicinally important compounds that specifically target B-cell receptor (BCR) pathways at various segments that have a major role in Bruton's tyrosine kinase (BTK) receptor, which belongs to the family of kinases. These kinases are usually situated close to the cell membrane due to which they participate in upstream processing of BCR signalling. Various molecules have been potentialized to target these signalling pathways of these kinase receptors in order to achieve a pharmacological effect. Given the central role of BTK in immunity, BTK inhibition represents a promising therapeutic approach for the treatment of multiple diseases. BTK inhibitors work by regulating B-cell receptor signalling along with inflammatory pathways and immune cell interactions, offering more advanced treatment options compared to traditional therapies. In addition to BTK inhibitors, an extensive knowledge of the pharmacological mechanisms underlying the blockage of these receptors is necessary in order to more accurately forecast when and where a patient could need combination therapy or just one medication. Efforts have been made to facilitate translational discoveries, drug re-purposing concepts, and further development of precision medicine products. This thorough literature study has focused on studies published until June 2025.

Introduction: Breast cancer is a widespread and life-threatening disease. While FDAapproved anti-BC drugs have improved survival rates, issues like drug resistance and adverse effects highlight the need for new therapeutic options. Molecular hybridization, a modern drug discovery strategy, combines different pharmacophores or frameworks into a single molecule to enhance pharmacological activity and improve treatment outcomes. Hybridizing two or more heterocyclic moieties has become a promising approach in anti-cancer drug discovery.

Methods: This article reviews the role of heterocyclic hybrids in BC therapy, based on literature from 1995 to 2024 available in PubMed. Key heterocyclic hybrids, pyrimidine, triazole, indole, coumarin, beta-carboline, azepine, isoquinoline, benzoxepine, and platinum-core hybrids were included.

Results: Triazole, in particular, was found to be a highly effective scaffold for BC treatment when combined with indole, pyridazinone, and steroid pharmacophores.

Discussion: The article discusses novel molecular hybridization strategies, current BC treatment options, clinical studies, key functional groups, anti-apoptotic mechanisms, and protein-ligand interactions. Structure-activity relationships are explored to highlight desirable pharmacophoric features, aiding in the development of more effective BC therapies.

Conclusion: Each heterocyclic hybrid class of BC comprises some salient features and potentials, which may be further investigated to obtain novel effective heterocyclic hybrid molecules in BC therapy.

Inflammation is a key contributor to the pathophysiology of various chronic diseases, including cancer, arthritis, cardiovascular disorders, chronic wounds, and gastrointestinal conditions, many of which rank among the leading causes of mortality worldwide, according to the WHO. The prevalence of chronic inflammation-related diseases is projected to rise steadily over the next 30 years, with an estimated three out of five individuals dying daily as a result of such conditions. Consequently, there is a growing demand for the discovery of novel anti-inflammatory agents. Cyclooxygenases play a pivotal role in inflammatory processes, being responsible for the synthesis of prostaglandins. COX-1 is constitutively expressed and primarily associated with "housekeeping" physiological functions, whereas COX-2 is an inducible isoform involved in inflammatory responses. Due to its role in inflammation and relatively favorable gastric safety profile compared to traditional NSAIDs, COX-2 has emerged as a significant therapeutic target for inflammation-related disorders. However, the increased risk of stroke and heart attack associated with COX-2 inhibitors has led to the withdrawal of several approved COX-2-targeting drugs from the market. Consequently, the development of new COX-2 inhibitors with potent efficacy and minimal cardiovascular side effects is of critical importance. This review explores a range of oxygen- and nitrogen-containing heterocycles as potential anti-inflammatory agents, emphasizing their COX-2 inhibitory activity, structure-activity relationships, and interactions within the COX-2 active site, as reported in recent studies. The article covers research findings published from 2019 through the first quarter of 2025.