Current medicinal chemistry最新文献

Understanding and managing pain in patients with terminal cancer is a vital aspect of palliative care, aimed at relieving suffering and improving quality of life in the final stages of illness. Studies indicate that approximately 50% of patients with stage 4 cancer report moderate to severe pain, with a quarter experiencing severe cancer-related pain. Despite opioid prescriptions in 97% of cases, a significant portion of patients continues to suffer unresolved pain during the last week of life. Cancer-related pain is multifaceted, often involving nociceptive, neuropathic, and mixed elements, necessitating a thorough, multidimensional approach to both assessment and treatment. The challenge of opioid tolerance and the potential for addiction demands careful monitoring. Interventional therapies, including nerve blocks and spinal cord stimulation, are gaining attention as valuable complements or alternatives to opioid use. Additionally, alternative methods like yoga, special diets, and food supplements provide diverse options for managing pain. Psychological therapies, including cognitive-behavioral techniques and mindfulness, address the mental and emotional dimensions of pain. Emerging technologies, including artificial intelligence, hold promise for optimizing pain management in terminal cancer care. This review explores advanced pain management strategies, focusing on traditional opioid therapies, modern pharmaceutical innovations, and non-pharmacological approaches such as alternative medicine, massage, dietary interventions, and psychological therapy.

Atherosclerosis is a complex multifactorial process that occurs in the vascular wall over many years and is responsible for a number of major diseases that affect quality of life and prognosis. A growing body of evidence supports the notion that immune mechanisms underlie atherogenesis. Macrophages are considered one of the key participants in atherogenesis, but their role in this process is multifaceted, which is largely due to the peculiarities of their cellular metabolism. Glycolysis is not only an important metabolic pathway in macrophages, but is also associated with their immune functions. Glycolysis in macrophages has complex regulatory pathways and is cross-linked with nitric oxide, which together determine the immune function of these cells. Thus, the immune and metabolic links underlying atherogenesis are of research and clinical interest in terms of their potential therapeutic opportunities.

Phytosomes are innovative compounds that enhance the bioavailability of plant-derived compounds, making them more effective in pharmaceuticals and nutraceuticals. By improving cellular absorption, phytosomes allow lower doses of plant extracts to achieve therapeutic effects, which may reduce both cost and the risk of potential side effects. The incorporation of phospholipids in phytosomes not only stabilizes the active compounds but also protects them from degradation in the gastrointestinal tract, potentially increasing their shelf life and efficacy. Despite their promise, more clinical trials are essential to fully validate the safety and therapeutic benefits of phytosomes. Ongoing research and developments may lead to a better understanding of their mechanisms of action and safety profiles and broaden their application in medicine.

Curcumin is a natural plant pigment that has been widely used in food production, drug development, and textile engineering. Gaining a deep understanding of the biological activities of curcumin and obtaining high-purity curcumin are of vital importance for basic research and applications of curcumin. In this review, we summarize recent advances in curcumin, mainly focusing on the methods of extracting and purifying curcumin from turmeric as well as applications based on biological activity. We systematically describe the advantages and disadvantages of traditional and modern extraction technologies. The usual purification methods include conventional methods (such as macroporous resin column chromatography and silica gel column chromatography, etc.) and auxiliary modern technologies (such as high-speed countercurrent chromatography and supercritical fluid chromatography). In terms of biological activity, the phenolic hydroxy group and methoxy group of curcumin are closely related to its antioxidant activity, endowing it with strong antibacterial, anti-inflammatory, and antitumor properties. Moreover, the development direction based on its multiple biological activities is also discussed.

Large-scale infectious diseases have become a significant threat to human health and safety. The successful invention of vaccines is the most powerful means for preventing infectious diseases and has greatly improved global human health. Even during the pandemic of COVID-19, which has affected the world, vaccines have played an irreplaceable role. Microneedles (MNs) punctured the stratum corneum and formed microchannels in the skin allowing the vaccine to be efficiently recognized by the abundant antigen-presenting cells (APCs) in the skin to form specific immunity. Compared with traditional vaccination methods, MN transdermal immunization has the advantages of painlessness, easy storage, and efficient immune response. In this review, we summarize the types of vaccines, types of MNs, research progress and clinical research status of MN-based vaccines. We also cover various technologies for vaccine encapsulation, stable delivery of MN vaccines, and a wide range of potential clinical applications. We also outline the future development prospects of the MN system onboard to achieve better clinical benefits.

Plumbagin (PL) is an important natural active ingredient in traditional Chinese medicine derived from the Plumbago zeylanica L. It possesses a variety of biological activities, such as anti-inflammatory, anticancer, antioxidant, antimicrobial, and neuroprotective properties, and has great potential for utilization in disease treatment and prevention. Cancer and neurological and psychiatric diseases are two major categories of diseases that currently threaten the physical and mental health of human beings, and their increasing incidence is causing a serious economic burden to all humanity. Based on the physical and chemical properties and pharmacokinetics of plumbagin, this study will focus on summarizing the application research status of plumbagin in cancer, neurological, and psychiatric diseases and analyze the molecular targets and action pathways of its therapeutic efficacy. This study will also briefly summarize the application of plumbagin in other diseases, as well as the existing problems and future development direction of plumbagin in clinical application, aiming to provide new perspectives and strategies for the development of new drugs and the treatment of existing diseases.

Background: The search for effective painkillers has led to intensive research, with a particular focus on the transient receptor potential vanilloid-1 (TRPV1) channel as a possible target.

Methods: One promising candidate is ononin, which is investigated for its binding with TRPV1 through a 200-ns molecular dynamic simulation and analysed via root-meansquare deviation (RMSD), root-mean-square fluctuation (RMSF), hydrogen-bond interactions, radius of gyration (RadGyr), and MM-PBSA energy calculations. The results were further validated experimentally via calcium imaging studies.

Results: Molecular dynamics revealed that the ononin-TRPV1 complex achieved stable binding within a remarkably short time of approximately 38 ns while maintaining the degree of compactness of the receptor throughout a 200 ns simulation period. In contrast, the capsazepine-TRPV1 complex displayed more significant structural deviations during the whole simulation. Moreover, MM-PBSA energy calculations showed a relatively strong binding affinity between ononin and TRPV1, mainly attributed to favourable hydrophobic interactions. Pre-incubation of dorsal root ganglia (DRG) neurons with ononin (1 and 10 μM) or capsazepine (10 μM) for 4 min prior to stimulation with capsaicin significantly reduced capsaicin-evoked calcium responses. No significant difference between capsazepine and ononin was found at a concentration of 10 μM.

Conclusion: Overall, this research demonstrates the potential of ononin as a potential antagonist for developing analgesics targeting TRPV1. Hence, and to our best knowledge, this study represents the first report of ononin's antagonistic activity towards TRPV1.

Background: Lung cancer (LC) is the second most lethal cancer and efficient treatments are missing. Our understanding of the underlying pathogenic mechanisms remains limited. Oridonin is a compound extracted from the Chinese herb Rabdosia rubescens with anticancer properties. Nevertheless, its effects on LC and the underlying mechanisms remain unknown.

Methods: In the current research, A549 and Hcc1833 cells were treated with different doses of oridonin, and cell proliferation and migration were detected using CCK8, EdU, Transwell, and wound healing assays. A subcutaneous tumor and caudal vein metastasis model was generated to verify the inhibitory effects of oridonin on Hcc1833 tumor growth and metastasis in vivo. Proteomics analyses then were performed to examine the regulatory mechanism. LiP-SMap combined with microscale thermophoresis and molecular docking analyses were used to validate the relationship between oridonin and S100A11.

Result: Data showed that oridonin suppressed cell proliferation and migration depending on dose and suppressed tumor growth and invasion. LiP-SMap and molecular docking analyses confirmed that oridonin interacted with the Asn-53 residue of S100A11, which inhibited the activation of oridonin. S100A11 overexpression reversed the inhibitory effects of oridonin on cell proliferation and migration.

Conclusion: In conclusion, the data indicate that oridonin suppresses LC malignant progression by targeting S100A11.

Alzheimer's disease (AD) remains a significant challenge in neurology, marked by progressive cognitive decline and neurodegeneration. Despite extensive research efforts, effective treatments are still lacking. Traditional drug discovery is often slow and costly, frequently resulting in limited success. Drug repurposing, which identifies new therapeutic uses for existing medications, has emerged as a promising approach to expedite AD treatment development. This review examines the potential of drug repurposing to transform AD therapy by utilizing the established safety profiles and known mechanisms of current drugs. We explore various repurposed drugs under investigation for AD, originally intended for cardiovascular, metabolic, and psychiatric conditions. Detailed discussions include how these drugs provide neuroprotective benefits by inhibiting amyloid-beta aggregation, reducing tau phosphorylation, and modulating neuroinflammation. Additionally, we emphasize the benefits of drug repurposing, such as shortened development timelines, lower costs, and increased chances of clinical success. By integrating current research findings, this review offers a thorough overview of the most promising repurposed drug candidates and their potential impact on AD treatment strategies. It stresses the importance of innovative approaches in AD research and calls for greater investment in drug repurposing initiatives. Through these strategies, we aim to accelerate the availability of effective treatments, providing renewed hope and a brighter future for those affected by this devastating disease.