Current pharmaceutical design最新文献

{"title":"Recent Developments in the Synthesis of Benzothiazoles and their Anti-cancer Mechanistic Discoveries.","authors":"Wafaa A Zaghary, Galal H Elgemeie, Rasha A Azzam, Safa A Aljuhr, Tamer M Sakr","doi":"10.2174/0113816128355783250212043621","DOIUrl":"https://doi.org/10.2174/0113816128355783250212043621","url":null,"abstract":"<p><p>Benzothiazole derivatives have garnered considerable attention owing to their versatile chemical scaffold and remarkable biological activities. The article provides an in-depth analysis of the diverse structural modifications and strategies employed to enhance the anticancer potential of these compounds from the period of 2020 to 2024. It discusses the role of structure-activity relationships (SAR) and computational approaches in optimizing benzothiazole derivatives for selective and effective cancer treatment.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Molecular Mechanisms of Natural Medicinal Active Ingredients Interfering with Male Fertility.","authors":"Wen-Wen Zhao, Liu Yang, Ye-Bin Yang, Ran Guo, Xing-Sheng Xiao, Yi-Min Cheng","doi":"10.2174/0113816128356183250207105548","DOIUrl":"https://doi.org/10.2174/0113816128356183250207105548","url":null,"abstract":"<p><p>The challenges posed by excessive global population growth remain significant. Hormonal female contraceptive pills, which have been approved for over 60 years, serve as an important means of contraception; however, many women experience adverse effects after taking these pills, including abnormalities in blood clotting, dizziness, headaches, and vomiting. In this context, male contraceptives have emerged as a prominent area of research. Unfortunately, most male contraceptives are still in the experimental or clinical research stages. Therefore, screening for active ingredients that can specifically inhibit sperm function from natural drug active ingredient libraries holds substantial clinical and practical significance. In this manuscript, we review the inhibitory effects of various natural drug active monomers on sperm function and their underlying molecular mechanisms, aiming to provide theoretical insights for the future development of novel male contraceptives.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nutraceutical Interventions for Mitigating Skin Ageing: Analysis of Mechanisms and Efficacy.","authors":"Mohammad Ibrahim, Harpreet Singh, Mohd Fahim, Shabina Khan, Jalaluddin Khan, Jagdish Kumar Arun, Arun Kumar Mishra, Tarun Virmani, Ashwani Sharma, Girish Kumar, Dalapathi Gugulothu, Shivani Chopra, Hitesh Chopra","doi":"10.2174/0113816128336661250218080928","DOIUrl":"https://doi.org/10.2174/0113816128336661250218080928","url":null,"abstract":"<p><p>Skin ageing is influenced by intrinsic factors such as genetics and hormones, as well as extrinsic factors like environmental exposure, ultraviolet (UV) radiation, and diet. These factors lead to biochemical, biological, and structural changes in the skin. Plant-derived compounds with antioxidant and anti-inflammatory properties have emerged as potential anti-ageing agents. This comprehensive review, spanning data from 1997 to 2024, explores the role of nutraceuticals in skin anti-ageing. The research data were drawn from Google, PubMed, PubMed Central, Scopus, and various journal databases, including ScienceDirect, Springer, and Taylor & Francis. This review specifically examines plant-derived polyphenols, carotenoids, and other bioactive compounds, analysing their mechanisms through signalling pathways and cellular processes, using data from in vitro, in vivo, and clinical studies. Polyphenols like quercetin, curcumin, and epigallocatechin gallate (EGCG) have antioxidant and anti-inflammatory properties, helping to reduce oxidative stress, inflammation, UV-induced collagen degradation, and inflammatory cytokines. Notably, curcumin enhances collagen production and decreases the number of senescent cells. Carotenoids such as β-carotene, lutein, zeaxanthin, and lycopene protect against UV damage, and lycopene-rich tomato paste was specifically noted for its ability to reduce erythema and DNA damage. Additionally, compounds like resveratrol, fisetin, and wogonin exert protective effects against oxidative stress and inflammation, with resveratrol improving collagen synthesis and reducing the appearance of wrinkles. These plant-derived compounds can effectively combat skin ageing through various mechanisms, including the inhibition of oxidative stress, inflammation, and extracellular matrix degradation. They present a natural and sustainable approach to skincare in accord with the growing trend of conscious consumption. Future research should focus on understanding the long-term effects and determining the optimal dosage for clinical applications, highlighting the potential of integrating plant-based nutraceuticals into skincare regimens.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the Effect of Rose Oxide in Animal Models of Paclitaxel-induced Neuropathic Pain in Rats.","authors":"Ana Marieta Fernandes Moreira, Boris Timah Acha, Tiberio Cesar Meneses de Oliveira Sinimbu, Suellen Aparecida Patricio Pereira, Fernanda Regina de Castro Almeida, Antonio Guilherme Silva Santos, Luciano da Silva Lopes, Anderson Nogueira Mendes, Maria de Lourdes Ferreira Meneses Dos Santos","doi":"10.2174/0113816128327126250220093640","DOIUrl":"https://doi.org/10.2174/0113816128327126250220093640","url":null,"abstract":"<p><strong>Introduction: </strong>Neuropathy caused by chemotherapy, a dose-limiting neurotoxic side effect, often leads to treatment discontinuation. About 30 to 70% of patients treated with paclitaxel experience peripheral neuropathy due to the drug combination and dosage. Given the significant prevalence of neuropathy in individuals who have undergone chemotherapy treatments and the growing need for new therapeutic approaches, including those based on natural resources, it is imperative to investigate substances capable of mitigating this adverse effect.</p><p><strong>Method: </strong>Natural plant compounds are often used to treat various pathological conditions due to superior treatment options and minimal side effects. Rose oxide (RO), monoterpenes present in several essential oils, have demonstrated anti-inflammatory activity by inhibiting IL-1β production and leukocyte migration. Therefore, the present study aimed to investigate the effect of rose oxide in its free form on animal models of neuropathic pain induced by antineoplastics in rats. Neuropathic pain was induced by paclitaxel at a dose of 20 mg/kg i.p. for four consecutive days and treated with rose oxide at doses of 12.5, 25, and 50 mg/kg and after this period, behavioral analyzes (von Frey mechanical allodynia, acetone test and open field), biochemical, hematological and assessment of oxidative stress (malondialdehyde levels). The results suggested that rose oxide has antinociceptive activity in animal models of antineoplastic-induced neuropathic pain in rats.</p><p><strong>Results: </strong>Furthermore, treatment with rose oxide did not show significant adverse effects on biochemical and hematological parameters, with the exception of the 12.5 mg/kg dose of RO affected creatinine levels and all doses of TGP, while the highest dose (50 mg/kg) caused changes in total proteins and albumin, suggesting a more binding strong with plasma proteins. Finally, treatment with RO 25 mg/kg significantly altered malondialdehyde (MDA) levels.</p><p><strong>Conclusion: </strong>These results suggest that the use of rose oxide in its free form may be a promising option for the treatment of antineoplastic-induced neuropathic pain in humans. However, further studies are needed to confirm these findings and evaluate safety and efficacy.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Esketamine Regulates Mitophagy through ULK1/FUNDC1 Signaling Pathway to Improve LPS-induced Acute Respiratory Distress Syndrome.","authors":"Mei Ding, Ping Pei, Weihua Liu, Yingli Cao, Yiqi Weng, Wenli Yu","doi":"10.2174/0113816128361112250221065359","DOIUrl":"https://doi.org/10.2174/0113816128361112250221065359","url":null,"abstract":"<p><strong>Background: </strong>As a heterogeneous clinical syndrome, acute respiratory distress syndrome (ARDS) is caused by infection-associated inflammation with limited treatment options. Esketamine possesses antiinflammatory properties, and it is effective in treating lung diseases.</p><p><strong>Objective: </strong>This study aimed to unveil the efficacy and mechanism of esketamine in ARDS.</p><p><strong>Methods: </strong>Lipopolysaccharide (LPS) is widely used to induce inflammatory response in lung injury. The mice model of ARDS in this study was established through the inhalation of LPS. Hematoxylin-eosin (H&E) staining was used to evaluate the pathological changes in the lung tissues of ARDS mice, and the histological index of lung damage was employed. Bicinchoninic acid (BCA) assay kits were utilized to assess the total proteins in bronchoalveolar lavage fluid (BALF), and a hemocytometer was used to count the number of total cells. The pulmonary vascular permeability was detected using Evans blue staining. Western blot was carried out to detect the expressions of tight junction proteins, and enzyme-linked immunosorbent assay (ELISA) detected the release of inflammatory cytokines in BALF and serum. Dihydroethidium (DHE) staining was used to detect reactive oxygen species (ROS) production, and the levels of myeloperoxidase (MPO) and oxidative stress markers were measured using corresponding assay kits. Apoptosis was assessed through terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and Western blot. Immunostaining detected the FUN14 domain-containing 1 (FUNDC1) and light chain 3B (LC3B) in lung tissues, and the expressions of autophagy-related proteins were detected using Western blot.</p><p><strong>Results: </strong>Our data showed that esketamine treatment alleviated LPS-stimulated lung damage, improved pulmonary vascular permeability, and inhibited inflammatory response, oxidative stress, and apoptosis in ARDS mice. Mechanically, esketamine activated mitophagy through UNC-52-like kinase 1 (ULK1)/FUNDC1 signaling pathway. These findings, for the first time, revealed the therapeutic potential of esketamine in treating ARDS.</p><p><strong>Conclusion: </strong>Collectively, this study revealed the protective role of esketamine against lung injury, inflammation, oxidative stress, and apoptosis in mice with ARDS and revealed the reaction mechanism related to mitophagy.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging AI and Natural Compounds: Innovative Approaches in the Diagnosis and Treatment of Hepatocellular Carcinoma.","authors":"Mohd Suhail, Mohammad Tarique, Shams Tabrez, Darshan Badal","doi":"10.2174/0113816128364693250117060342","DOIUrl":"https://doi.org/10.2174/0113816128364693250117060342","url":null,"abstract":"<p><p>Liver cancer, particularly Hepatocellular Carcinoma (HCC), remains a significant global health challenge owing to its high incidence and position as the fourth leading cause of cancer-related mortality. HCC represents 75-85% of all liver cancer cases and ranks as the sixth most prevalent cancer globally. Several factors, including late-stage diagnosis, limited treatment effectiveness, resistance to conventional therapies, and adverse side effects, hinder the delivery of life-prolonging care to patients with HCC. Current treatment options such as chemotherapy, immunotherapy, and adjuvant therapy are often associated with severe side effects. Consequently, there is an urgent need for improved diagnostic methods and alternative therapeutic approaches to extend life expectancy and reduce HCC-related mortalities. Artificial Intelligence (AI) is an emerging technology that offers promising advances for the early detection of HCC. In terms of alternative treatments, natural compounds have garnered significant attention because of their diverse biological activities, such as antitumor, antiviral, antimicrobial, antioxidant, anti-inflammatory, hepatoprotective, antimutagenic, and cardioprotective effects, and their relatively lower side effect profiles. These compounds exhibit hepatoprotective properties by modulating key molecular pathways involved in HCC development and progression. This article provides an overview of recent advances in the understanding of liver cancer etiology, therapeutic targets in HCC pathogenesis, the role of AI in its detection, and the potential of natural products, particularly flavonoids, as preventive and therapeutic agents against HCC, highlighting their underlying mechanisms of action.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Potential Mechanisms of Zuo Gui Pill for the Treatment of Knee Osteoarthritis Based on Network Pharmacology and Molecular Docking Techniques.","authors":"Yulin Wang, Jiahao Zhang, Junzheng Liu, Tun Liu, Jiaxin Zhao, Yiling Guo, Xinyi Zhang, Wei Wang","doi":"10.2174/0113816128330436250210052548","DOIUrl":"https://doi.org/10.2174/0113816128330436250210052548","url":null,"abstract":"<p><strong>Background: </strong>Zuo Gui pill (ZGP) is a herbal compound formulation used to treat knee osteoarthritis (KOA), but its underlying mechanisms are still unclear. This study aimed to initially elucidate the molecular mechanisms of ZGP in treating KOA using network pharmacology and molecular docking techniques.</p><p><strong>Methods: </strong>We collected information on the drug compounds and targets from TCMSP, HERB, BATMANTCM, and UniProt databases, as well as the KOA-related targets from DisGeNET, GeneCards, OMIM, and GEO databases. Afterward, we obtained the hub targets of ZGP and KOA. The biological processes and major pathways of the hub targets were analyzed by GO and KEGG, and three networks were constructed to illustrate the mechanisms of ZGP for the treatment of KOA. Finally, molecular docking was carried out to verify the binding of the main compounds to the key targets.</p><p><strong>Results: </strong>Through the network pharmacological analysis, we screened important compounds in ZGP, such as quercetin, kaempferol, wogonin, isorhamnetin, and 138 hub targets, including PTGS2, NOS3, AKT1, MAPK1, which are enriched in PI3K-Akt, MAPK, TNF, IL-17, HIF-1, and other signaling pathways. The molecular docking results showed that the main compounds and key targets have high affinity, which further demonstrated the molecular mechanisms and provided a basis for the clinical application of ZGP.</p><p><strong>Conclusion: </strong>This study illustrates the specific mechanisms of ZGP in the treatment of KOA using network pharmacology and molecular docking techniques, which lays the foundation for further research on its pharmacological mechanisms.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advancement in Drug Targeting Therapies in the Treatment of Pancreatic Cancer.","authors":"Ranjit K Harwansh, Junainah Abd Hamid, Pranay Wal, Rohitas Deshmukh, Pratap Kumar Patra, Amin Gasmi","doi":"10.2174/0113816128334659241223113743","DOIUrl":"https://doi.org/10.2174/0113816128334659241223113743","url":null,"abstract":"<p><strong>Objective of the study: </strong>This review aims to critically analyze the scope for targeting drugs towards the treatment of improving outcomes in PDAC, focusing on DNA repair inhibitors, antiangiogenic therapy, inhibitors of the KRAS pathway, anti-stromal, and nanoparticle-based therapy.</p><p><strong>Materials and methods: </strong>A critical review of preclinical and clinical studies was conducted to summarize the therapeutic interventions that target specific mutations in PDAC, components of the tumor microenvironment, and drug delivery systems, especially nanotechnology, to enhance targeting and efficacy.</p><p><strong>Results: </strong>Inhibitors and nanotechnology-based targeted therapies have reported promise in preclinical models: drug delivery is enhanced with the loss of PDAC resistance mechanisms. Formulations and combinations targeting KRAS as well as other pathways point toward improved drug delivery over 'orthodox' treatment approaches.</p><p><strong>Conclusion: </strong>This review concludes that although improvement in therapies for PDAC has incrementally been proven in recent literature, however, more research is expected to enhance these approaches so that they can be applied appropriately at the clinical stage. In future studies, it is expected to optimize treatment combinations, address mechanisms of resistance, and improve the delivery of drugs.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Review on Melanoma Brain Metastases.","authors":"Sabi Shrestha, Charles M Cook, Jay Parekh, Jane Mattei","doi":"10.2174/0113816128340742250118150157","DOIUrl":"https://doi.org/10.2174/0113816128340742250118150157","url":null,"abstract":"<p><p>Melanoma brain metastases (MBM) are associated with poor prognosis and remain a significant challenge in oncology. In recent years, significant progress has been made in understanding the molecular mechanisms underlying MBM. Advances in targeted therapies, immunotherapies, and stereotactic radiosurgery (SRS) have significantly improved patient survival. This study presents an overview of the current landscape of treatment approaches and emerging modalities for MBM treatment, highlighting recent advancements and future directions for research and clinical practice.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Potential of H2 Therapy in Reducing Surgical Complications: A Review on Anti-inflammatory, Antioxidant, and Anti-fibrotic Mechanisms.","authors":"Marzieh Neykhonji, Abdulridha Mohammed Al-Asady, Amir Avan, Majid Khazaei, Seyed Mahdi Hassanian","doi":"10.2174/0113816128354067250211052237","DOIUrl":"https://doi.org/10.2174/0113816128354067250211052237","url":null,"abstract":"<p><strong>Objective: </strong>This review demonstrates the potential role of hydrogen in post-surgical adhesion prevention and calls for further investigation of its molecular pathways, as well as clinical studies to assess its efficacy and safety in a therapeutic setting.</p><p><strong>Methods: </strong>PubMed and Google Scholar were extensively queried to investigate the potential role of hydrogen in preventing post-surgical adhesions and its underlying mechanisms.</p><p><strong>Results: </strong>Molecular hydrogen exhibits selective antioxidant, anti-inflammatory, and anti-fibrotic properties, holding potential for the treatment and prevention of various disorders, including acute pancreatitis, respiratory diseases, and ischemia-reperfusion damage conditions, among others. Postoperative adhesion is associated with chronic pain, organ dysfunction, and acute complications, fundamentally rooted in inflammation, oxidative stress, and fibrosis. The surgical injury initiates an inflammatory response characterized by immune cell mobilization and an increase in pro-inflammatory cytokine levels, thereby promoting adhesion formation.</p><p><strong>Conclusion: </strong>Hydrogen is demonstrated to attenuate the early inflammatory response by down-regulating proinflammatory cytokines alongside its anti-oxidative and anti-fibrotic effects. As a potential therapeutic agent for post-surgical adhesions, hydrogen warrants additional investigation to elucidate the exact molecular pathways responsible for its observed efficacy and safety.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}