Current topics in medicinal chemistry最新文献

Background: Prostate and pancreatic cancers pose significant global health challenges. This study explored the potential of compound 5b, a novel phthalimido-1,3-thiazole derivative, as an anticancer agent against these malignancies.

Methods: In vitro, compound 5b exhibited potent cytotoxic activity against both prostate (DU-145 and PC-3) and pancreatic (Panc-1 and Mia Paca-2) cancer cell lines. Notably, it significantly reduced colony formation in PC-3 cells, potentially hindering tumor growth. Furthermore, treatment with compound 5b suppressed cell migration and induced cell cycle arrest in the PC-3 line. Additionally, it triggered cell death through late apoptosis and necrosis at higher concentrations. Safety evaluations in mice revealed no mortality or adverse effects after a 30-day treatment with compound 5b. Key blood parameters (hematology) and biochemical markers of liver and kidney function remained unaltered.

Results: Compound 5b significantly reduced colony formation, suppressed cell migration, and induced cell cycle arrest and apoptosis/necrosis in prostate cancer cells. In vivo, safety evaluations showed no adverse effects in treated mice, with blood and biochemical markers remaining normal.

Conclusion: These findings suggest that compound 5b holds promise for further development as a therapeutic option for prostate and pancreatic cancers. Its multimodal activity profile, targeting cell viability, migration, cell cycle progression, and cell death, warrants further investigation.

Alzheimer's Disease (AD) is a complex neurological condition caused by various factors. Diet, oxidative stress, and the gut microbiota all play critical roles in the development of AD. Recent studies suggested a bidirectional relationship between the gut and the brain, emphasizing the pivotal role of the gut microbiome in influencing cognitive functions. For instance, dysbiosis, a disruption in the balance of gut microbial communities, has been linked to neuroinflammation and the accumulation of amyloid-beta plaques, hallmark features of AD. Oxidative stress, arising from an imbalance between free radicals and antioxidants, contributes significantly to AD pathology. The molecular mechanisms through which oxidative stress impacts neuronal health and exacerbates the cognitive decline in AD patients are also relevant. Moreover, nutritional interventions emerge as promising strategies to modulate these inflecting factors. Dietary components, such as antioxidants, omega-3 fatty acids, and polyphenols, exhibit neuroprotective effects, potentially mitigating AD progression. In contrast, the Western diet has a high potential to abet AD onset. Mediterranean diet and/or intermittent fasting are more valuable diets that may help delay the AD onset or progression. Limitations like individual differences affect the efficacy of nutritional interventions. As a supporting therapy, personalized diets should be applied according to the patients' special needs/microbiomes in the future. To gather current knowledge on the interconnected roles of the gut microbiome, oxidative stress, and nutritional interventions in AD is crucial. Understanding these interactions may pave the way for novel therapeutic approaches, as well as disputing the potential diets that can help improve AD patients' quality of life.

Introduction: The medicinal plants of Izki hold significant ethnopharmacological relevance, serving as primary healthcare resources for generations. These plants exhibit known pharmacological properties, making them crucial for traditional and modern therapeutic applications.

Objectives: The primary goal of this study was to record, conserve, and analyze the traditional knowledge of medicinal plants in Izki. It also aimed to evaluate the therapeutic potential of these plants for treating various ailments while identifying their pharmacological relevance for modern applications.

Materials and methods: The study involved interviews with 300 local residents to record their traditional knowledge of therapeutic herbs. Quantitative methods were employed. Plant specimens were collected, identified, and submitted to the herbarium.

Results: The study recorded 65 medicinal plants (22 cultivated, 43 wild) used for 62 disease categories. Eye diseases (0.721; 13 taxa) and bone fractures (0.700; 13 taxa) showed higher consensus among respondents. FL% analysis highlighted Tephrosia apollinea (69.2%), Trachyspermum ammi (62.5%), and Azadirachta indica (53.3%) as culturally significant. Rhazya stricta emerged as an antirheumatic agent, reflecting shared ethnobotanical practices between India and Oman. Plants like Rhazya stricta, Fagonia indica, Trachyspermum ammi, and Ziziphus spina-christi demonstrated consistent regional applications, underscoring their potential for pharmacological investigation.

Conclusion: This study underscores Izki's rich ethnobotanical knowledge, with extensive use of leaves, fruits, and whole plants for medicinal, dietary, and hygienic purposes. Conservation efforts, sustainable harvesting, and collaborations with pharmaceutical sciences are essential to validate the pharmacological potential of Rhazya stricta, Fagonia indica, Trachyspermum ammi, and Ziziphus spina-christi and bridge traditional knowledge with modern medicine.

Autophagy is a crucial mechanism that maintains cellular homeostasis and has emerged as a pivotal factor in cancer progression and drug resistance. Despite autophagic regulations being a complex process, convincing evidence shows that PI3K-Akt-mTOR, LKB1-AMPK-mTOR, and p53 pathways are the primary upstream regulators of the autophagy process. Currently, there is an immense amount of evidence demonstrating that autophagy plays a crucial role in cancer. It is worth noting that autophagy increases cancer cells' resistance to chemotherapy and anticancerous drugs. According to studies, cancer cells employ autophagy to evade the cytotoxic impacts of several anticancer drugs, resulting in autophagy-mediated drug resistance. This resistance brings a significant challenge to cancer management, emphasising the need for improved therapeutic strategies to overcome this obstacle and enhance the efficacy of cancer treatments. Therefore, this review gathers current data and findings to understand the intricate mechanism between autophagymediated drug resistance and cancer progression. Moreover, this study highlights the intriguing role of natural compounds and nano-formulations in combating autophagy-mediated drug resistance in various carcinomas, presenting a promising avenue for the effective management of cancer treatment.

Humans, animals, and plants possess small polypeptides known as antimicrobial peptides (AMPs), which are often positively charged. They are tiny, mostly basic peptides with a molecular weight of 2 to 9 kDa. They are a crucial part of plants' innate defense system, acting as effector molecules that provide a resistance barrier against pests and diseases. Plants have been found to contain antimicrobial peptides belonging to numerous families, including plant defensins, thionins, cyclotides, and others. An increase in pathogen resistance is achieved through the transgenic overexpression of the relevant genes, while pathogen mutants that are susceptible to peptides exhibit decreased pathogenicity. For many organisms, AMPs exhibit a wide range of antimicrobial activity against various pathogens and serve as a crucial line of defense. This review raises awareness about plant antimicrobial peptides (AMPs) as potential therapeutic agents in the pharmaceutical and medical fields, including treating fungal and bacterial diseases. It also provides a broad synopsis of the main AMP families found in plants, their mechanisms of action, and the factors that influence their antimicrobial activities.

Objective: The objective of this study is to investigate the differences in the therapeutic effects of recombinant GLP-2 and Lactobacillus plantarum L9, both alone and in combination, for treating UC, providing new directions for future acute UC therapy.

Methods: The GLP-2 homologous peptide from Amphiuma tridactylum species was screened via the NCBI database, and its advanced structure and molecular function were bioinformatically predicted. This fragment was then recombined into the plasmid pET-28a (+) and transformed into Escherichia coli Rosetta (BL21). IPTG induced the expression of the recombinant protein, which was purified, followed by thrombin cleavage to obtain Tuxtide peptides. These peptides were separated via Native PAGE and purified using Trition X-114 and dialysis methods. Acute UC model mice were established using 3% DSS. Changes in body weight and disease activity index scores during the medication period were recorded and analyzed. Colon length and spleen index of mice in each group were measured, and HE staining and colon histology scoring were performed. ELISA was used to detect myeloperoxidase and interleukin-1β in mouse colon tissue.

Results: Compared to the DSS group, the colon length of mice in all treatment groups improved, with significant effects observed in the Tuxtide and Tuxtide+L9 groups (P<0.05). Body weight in all treatment groups rebounded compared to the DSS group, and DAI scores decreased (P<0.05), with the Tuxtide group showing the best improvement in body weight. All treatment groups alleviated intestinal mucosal pathological damage to varying degrees compared to the DSS group, with the Tuxtide+L9 group showing the best anti-inflammatory effect, reducing colon histology scores and restoring intestinal crypts (P<0.1).

Conclusion: Both Tuxtide alone and in combination with Lactobacillus plantarum L9 can alleviate symptoms in mice with acute ulcerative colitis.

Cancer and Alzheimer's disease (AD) are among the most prevalent diseases in contemporary society, exerting profound psychological and physical distress on affected individuals and their kin. There is an emerging consensus from epidemiological studies suggesting a potential inverse relationship between the two conditions; that is, the presence of one disease might offer some level of protection against the other. The etiology of both cancer and AD is intricately linked to dysregulation and perturbations in critical signaling pathways. These pathways, along with the diverse factors they encompass, exert distinct influences on the pathogenesis of two diseases. In this paper, we make a short review of the different mutations in the relevant signaling pathways between cancer and AD and introduce a few representative drugs for the two diseases based on various targets to provide a new idea for treating cancer and AD.

Introduction: Healthcare organizations are complicated and demanding for all stakeholders, but artificial intelligence (AI) has revolutionized several sectors, especially healthcare, with the potential to enhance patient outcomes and standard of life. Quick advancements in AI can transform healthcare by implementing it into clinical procedures. Reporting AI's involvement in clinical settings is vital for its successful adoption by providing medical professionals with the necessary information and tools.

Background: This paper offers a thorough and up-to-date summary of the present condition of AI in medical settings, including its possible uses in patient interaction, treatment suggestions, and disease diagnosis. It also addresses the challenges and limitations, including the necessity for human expertise along with future directions. In doing so, it improves the understanding of AI's relevance in healthcare and supports medical institutions in successfully implementing AI technologies.

Methods: The structured literature review, with its dependable and reproducible research process, allowed the authors to acquire 337 peer-reviewed publications from indexing databases, such as Scopus and EMBASE, without any time restrictions. The researchers utilized both qualitative and quantitative factors to assess authors, publications, keywords, and collaboration networks.

Results: AI implementation in healthcare holds enormous potential for enhancing patient outcomes, treatment recommendations, and disease diagnosis. AI technologies can use massive datasets and recognize patterns to beat human performance in various healthcare domains. AI provides improved accuracy, reduced expenses, and time savings. It can transform customized medicine, optimize drug dosages, improve management of population health, set guidelines, offer digital medical assistants, promote mental health services, boost patient knowledge, and maintain patientclinician trust.

Conclusion: AI can be utilized to detect diseases, develop customized therapy plans, and support medical professionals with their clinical decision-making. Instead of just automating jobs, AI focuses on creating technologies that can improve patient care in several healthcare settings. However, challenges such as biasness, data confidentiality, and data quality must be resolved for the appropriate and successful integration of AI in healthcare.

Aim: To investigate the antimicrobial potential of methanol fruit extract of Solanum xanthocarpum against Methicillin-Resistant Staphylococcus aureus (MRSA) and elucidate its mode of action.

Background: The rise of antimicrobial resistance (AMR) demands the exploration of alternative therapeutic strategies to combat resistant pathogens.

Objective: To evaluate the efficacy of Solanum xanthocarpum methanol extract against MRSA, and identify its active constituents and mechanism of action.

Method: The fruits of Solanum xanthocarpum were extracted using various solvents, with hexane and methanol yielding the highest results. Microbroth dilution assays assessed antimicrobial activity, while in vitro assays such as Alamar blue, Scanning Electron Microscopy (SEM), protein, and nucleic acid leakage examined metabolic disruption and cell membrane integrity. Gas Chromatography- Mass Spectrometry (GC-MS) was used to identify active compounds, and molecular docking studies assessed interactions with key MRSA proteins.

Result: The methanol extract demonstrated significant antimicrobial activity against MRSA, causing metabolic disruption and leakage of cellular contents as evidenced by various in vitro assays including alarm blue, SEM, and protein and nucleic acid leakage assay. GC-MS analysis identified alpha-linoleic acid and palmitic acid as key active components. Molecular docking studies confirmed their inhibition of beta-lactamase activity, cell wall biosynthesis, efflux pumps, and virulence factors.

Conclusion: The findings suggest that Solanum xanthocarpum methanol fruit extract has promising potential as a natural remedy against AMR associated with MRSA.

Herein, we present an in-depth review focused on the application of different artificial intelligence (AI) approaches for developing protein kinase inhibitors (PKIs) targeting anticancer activity, focusing on how the AI-based tools are making promising advances in drug design and development, by predicting active compounds for essential targets involved in cancer. In this context, the machine learning (ML) approach performs a critical role by promoting a fast analysis of a thousand potential inhibitors within a small gap of time by processing large datasets of chemical data, putting it at a higher level than other traditionally used methods for screening molecules. In general, AI-based screening of compounds reduces the time of the work and increases the chances of success in the end. Additionally, we have covered recent studies focused on the application of deep neural networks (DNNs) and quantitative structure-activity relationships (QSAR) to identify PKIs. Furthermore, the paper covers new AI-based methodologies for filtering or improving datasets of potential compounds or even targets, such as generative models for the creation of novel compounds and ML-based strategies to collect information from different databases, increasing the efficiency in drug design and development. Finally, this review highlights how AI-based tools are increasing and improving the field of PKIs targeting cancer, making them an alternative for the future in the medicinal chemistry field.