Current topics in medicinal chemistry最新文献

{"title":"Neurological Inflammation in Parkinsonism: Current Prognosticative Diagnostics and Pitfalls.","authors":"Thangavel Lakshmipriya, Subash C B Gopinath, Yeng Chen, Sreenivasan Sasidharan, Evan T Salim, Makram A Fakhri","doi":"10.2174/0115680266365134250530063901","DOIUrl":"https://doi.org/10.2174/0115680266365134250530063901","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a persistent neurological degenerative condition that can significantly alter one's quality of life. This condition affects the substantia nigra, the region of the brain that contains dopamine-producing neurons. It is a disorder of the central nervous system that arises when nerve cells, or neurons, in this brain area are damaged or die. Norepinephrine, another chemical messenger that aids in controlling primary physiological processes, such as heart rate and blood pressure, is also deficient in PD patients. The symptoms of PD can interfere with daily activities and include fatigue, walking difficulties, limb rigidity, and loss of smell. Researchers are striving to identify a reliable biomarker for Parkinson's disease. Currently, the Food and Drug Administration has approved the radiotracer I-123-ioflupane injection followed by scanning (DATscan- SPECT) for precise analysis. To diagnose Parkinson's disease early, researchers are developing predictive diagnostic techniques using various biomarkers. The right biosensor can recommend the best personalized course of action to slow the progression of Parkinson's disease. This review highlights the strong performance of diagnostic biomarkers for Parkinson's disease and emphasizes the effectiveness of the common immuno-, apta- and DNA-sensors for their efficient implementations for different biomarkers. Further, it also discusses the potential advantages and drawbacks associated with detection methods for improving high-performance diagnostics.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224676","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":"An Updated Review on Nipah Virus Infection with a Focus on Encephalitis, Vasculitis, and Therapeutic Approaches.","authors":"Pratibha Pandey, Prashant Chauhan, Shivam Pandey, Sorabh Lakhanpal, G Padmapriya, Shivang Mishra, Mandeep Kaur, Ayash Ashraf, M Ravi Kumar, Seema Ramniwas, Fahad Khan","doi":"10.2174/0115680266347761250515082453","DOIUrl":"https://doi.org/10.2174/0115680266347761250515082453","url":null,"abstract":"<p><p>Nipah virus (NiV), a member of the Paramyxoviridae family, has gained global attention owing to its high mortality rate and destructive potential. NiV has a Biosafety Level 4 (BSL-4) rating and has repeatedly precipitated devastating outbreaks associated with severe respiratory infections, often accompanied by encephalitis and systemic vasculitis. Several studies have been conducted to understand the mechanisms involved in its pathogenesis and to effectively produce new medications to treat this zoonotic virus. However, the cruelty of NiV and its propensity to elude existing treatments underscores the need to elucidate better therapeutics to manage NiV infection more effectively. Therefore, this review highlights the fundamental mechanisms involved in the etiology of NiV, specifically fatal encephalitis and systemic vasculitis. Furthermore, this study investigated promising therapeutic strategies to mitigate the clinical consequences of NiV infections.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224675","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":"Unraveling Neurodegenerative Disorders: The Potential of Indole and Imidazole-Based Heterocycles.","authors":"Riya Shikha, Deepak Kumar, Mohd Qasid Lari, Astik M Ashesh, Pranay Wal, Bhupendra Singh, Shailendra Pandey, Dileep Kumar, Ajay Kumar","doi":"10.2174/0115680266356937250527075734","DOIUrl":"https://doi.org/10.2174/0115680266356937250527075734","url":null,"abstract":"<p><p>Neurodegenerative diseases present a considerable challenge to healthcare systems worldwide, prompting the exploration of innovative treatment strategies. Heterocyclic compounds, specifically those originating from the indole and imidazole structures, have garnered increasing interest due to their potential to protect neurons. Based on an in-depth literature survey in this review, we have compiled various derivatives of indole and imidazole scaffolds with potential in neurodegenerative disorders. This review also emphasized the Structure-Activity Relationship (SAR) and pharmacokinetics to reveal the active pharmacophores of various indole and imidazole analogs. We delve into the underlying molecular and cellular mechanisms involved in neurodegeneration, highlighting how indole and imidazole derivatives exert neuroprotective effects by modulating oxidative stress, inflammation, protein misfolding, inhibiting cholinesterase, and neuroinflammation. Finally, we address the challenges and prospects in translating these findings into clinical therapies, underscoring the need for continued research to optimize the safety and efficacy of heterocyclic compounds in the treatment of neurodegenerative disorders.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207961","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":"Therapeutic Potential of Genistein: Insights into Multifaceted Mechanisms and Perspectives for Human Wellness.","authors":"Lakhyajit Borah, Saikat Sen, Manjit Mishra, Pervej Alom Barbhuiya, Manash Pratim Pathak","doi":"10.2174/0115680266377646250527075042","DOIUrl":"https://doi.org/10.2174/0115680266377646250527075042","url":null,"abstract":"<p><strong>Background: </strong>Genistein, a natural isoflavonoid found predominantly in legumes and soy-based foods, has garnered significant attention due to its multifaceted mechanisms and potential therapeutic applications. Chemically, genistein is a 4',5,7-Trihydroxyisoflavone having a molecular formula of C15H10O5, which enables its interactions with diverse biological targets.</p><p><strong>Objective: </strong>The main objective of this review is to summarize the pharmacological effects of genistein, elucidating its potential mechanisms of action. Furthermore, the review emphasizes genistein's impact on human health when used as a dietary supplement.</p><p><strong>Methods: </strong>The authors have gone through a vast number of article sources from various scientific databases like Google Scholar, PubMed and Web of Science.</p><p><strong>Results: </strong>Genistein exhibits antioxidant properties by countering free radicals and reducing lipid peroxidation. Genistein's anti-inflammatory effects involve inhibiting proinflammatory pathways and cytokine production. Notably, it shows anticancer potential against various malignancies by promoting apoptosis, inhibiting angiogenesis, and hindering metastasis. Moreover, genistein has antidiabetic properties, enhancing insulin secretion, protecting β-cells, and improving glucose tolerance. Its antiviral and antibacterial actions contribute to inhibiting pathogen growth and viral replication. Genistein accelerates wound healing by minimizing oxidative stress, facilitating reepithelialization, and suppressing inflammation. Its potential in peptic ulcer treatment is supported by anti-inflammatory and antioxidant effects. Hepatoprotective activities include inhibiting lipid peroxidation, bolstering antioxidant defences, and modulating metabolic enzymes. Furthermore, genistein positively impacts the immune response, influencing cytokine levels, lymphocyte proliferation, and interferon production.</p><p><strong>Conclusion: </strong>Genistein's multifaceted pharmacological activities render it a promising dietary supplement with implications for diverse health conditions, warranting further comprehensive research to optimize its clinical utility.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207960","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":"Advances in the Directed Evolution of Computer-aided Enzymes.","authors":"Zhiming Hu, Yijie Liu, Yonghong Huang, Peng Yu","doi":"10.2174/0115680266377310250526045137","DOIUrl":"https://doi.org/10.2174/0115680266377310250526045137","url":null,"abstract":"<p><p>Experimental-driven directed evolution has achieved remarkable success in enzyme engineering. However, it relies on random mutagenesis and high-throughput screening, both of which have certain limitations, particularly the randomness of mutagenesis and the extensive screening workload that slows down the method's rapid development. In contrast, computer-aided directed evolution combines computational simulations with experimental techniques, providing an efficient and precise approach to enzyme rational design and optimization. By integrating computational tools, researchers can streamline the enzyme design process, improving the accuracy of mutations and screenings, which in turn accelerates enzyme optimization. This review comprehensively introduces the commonly used methods and applications of computer-aided directed evolution, discussing the tools and techniques frequently used in protein sequence analysis and structural analysis. It also covers computational simulation and prediction strategies such as homology modeling, molecular docking, molecular dynamics simulations, machine learning algorithms, and virtual screening. These tools play a critical role in predicting the effects of mutations on enzyme function and optimizing enzyme performance. Moreover, the review explores widely adopted semi-rational and rational design strategies in enzyme engineering, which combine computational predictions with experimental validation to effectively improve enzyme performance. Additionally, the article delves into the challenges and bottlenecks encountered in applying computational technologies in directed evolution, including issues related to computational precision, data quality, and the complexity of enzyme-substrate interactions. Despite these challenges, the future of computer-aided directed evolution holds great promise, with advancements in computational power, machine learning, and multi-omics data integration offering tremendous potential to overcome current limitations. In conclusion, this review aims to provide valuable insights for researchers in enzyme engineering, assisting them in developing new, efficient enzymes by integrating both experimental and computational approaches.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198427","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":"Prescription FINO2 and Pirfenidone Supported in Reducing Fibrosis in Mouse Breast Tumor Tissue by Targeting SLC7A11 and HMOX1.","authors":"Azita Mohammadbeygi, Gholamreza Nikbakht Brujeni, Zohre Eftekhari, Negar Panahi Kazerouni","doi":"10.2174/0115680266353809250526084207","DOIUrl":"https://doi.org/10.2174/0115680266353809250526084207","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer has become the most commonly diagnosed cancer worldwide and represents a major burden to public health. Advances in understanding ferroptosis pathways and identifying new therapeutic targets raise hope for using ferroptosis modulators to treat untreatable diseases.</p><p><strong>Methods: </strong>In this study, BALB/c mice were divided into several groups: model, Doxorubicintreated, FINO2-treated, Pirfenidone-treated, and a combined Pirfenidone + FINO2 group. After treatment, we assessed iron content in cancer cells, fibrosis area, CD34 expression, and mRNA levels of solute carrier family 7 member 11(SLC7A11) and heme oxygenase 1 (HMOX1).</p><p><strong>Results: </strong>Results showed that the average tumor size in the Pirfenidone + FINO2 group was significantly smaller than in the doxorubicin group. Treatments with FINO2, Pirfenidone, or their combination significantly increased iron content in cancer cells and reduced the fibrosis area. Cotreatment with FINO2 and Pirfenidone also led to notable decreases in CD34 expression and mRNA levels of SLC7A11 and HMOX1.</p><p><strong>Conclusion: </strong>These findings suggest that FINO2 ferroptosis agonists, when combined with other anticancer agents like Pirfenidone, can enhance ferroptosis and reduce tumor fibrosis. Additionally, the overexpression of SLC7A11 and HMOX1 in breast cancer model mice is associated with increased tumor growth and reduced metastasis, indicating that targeting these proteins with specific inhibitors may be a promising strategy for breast cancer treatment.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198428","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":"Tomatidine Attenuates C48/80-induced Inflammatory Responses in HMC-1 Cells and is Associated with Modulation of the JNK/AP-1/NF-κB/Caspase-1 Pathway.","authors":"Xiyan Xiao, Shiyin Yang","doi":"10.2174/0115680266392868250527045507","DOIUrl":"https://doi.org/10.2174/0115680266392868250527045507","url":null,"abstract":"<p><strong>Background: </strong>Existing research has suggested that the JNK/AP-1/NF-κB/Caspase-1 pathway may account for the activation of HMC-1 mast cells under inflammatory circumstances, and our current study aims to validate whether Tomatidine could act as the candidate to modulate this pathway in Allergic Rhinitis (AR).</p><p><strong>Objective: </strong>This study aimed to characterize the effect of Tomatidine on inflammation in C48/80- activated HMC-1 cells in vitro and to explore the underlying mechanisms involved.</p><p><strong>Methods: </strong>The inflammation in HMC-1 cells was triggered via C48/80 induction to mimic the AR, and the effects of Tomatidine on the viability of HMC-1 cells were tested using the Cell Counting Kit-8 assay. Thereafter, the concentrations of inflammation-related cytokines, Interleukin-1β, tumor necrosis factor-α, as well as the histamine and β-hexosaminidase, were quantified by enzymelinked immunosorbent assay. The activation status of the JNK/AP-1/NF-κB/Caspase-1 pathway in HMC-1 cells following C48/80 and/or Tomatidine intervention was determined based on immunoblotting assay.</p><p><strong>Results: </strong>The viability was elevated in HMC-1 cells following C48/80-induced activation, and the concentration of inflammation-related cytokines and mediators was increased as well. Meanwhile, the protein levels of active Caspase-1 and the phosphorylation of JNK/AP-1/NF-κB/Caspase-1 pathway-related proteins were also observed in HMC-1 cells after the treatment of C48/80. On the contrary, Tomatidine intervention suppressed the viability and the concentration of inflammationrelated cytokines and mediators of modeled HMC-1 cells and led to the inactivation of the JNK/AP-1/NF-κB/Caspase-1 pathway in modeled HMC-1 cells.</p><p><strong>Conclusion: </strong>Our study demonstrates that Tomatidine can attenuate C48/80-induced inflammatory responses in HMC-1 cells in vitro, potentially through modulation of the JNK/AP-1/NF- κB/Caspase-1 signaling pathway. These findings provide preliminary evidence supporting Tomatidine as a candidate for further investigation in allergic inflammation.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186696","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":"Design, Synthesis, Molecular Docking, and Biological Evaluation of 7-Phenyl-5-(thiophen-2-yl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-diones as Antibacterial Agents.","authors":"Mallika Agrawal, Adarsh Kumar, Ankit Kumar Singh, Harshwardhan Singh, Balasubramanian Narasimhan, Pradeep Kumar","doi":"10.2174/0115680266355090250407105802","DOIUrl":"https://doi.org/10.2174/0115680266355090250407105802","url":null,"abstract":"<p><strong>Background: </strong>New antibacterial agents are urgently needed as bacterial diseases, especially urinary tract infections (UTIs), are becoming more common, and antibiotic resistance is increasing.</p><p><strong>Aims: </strong>This study aimed to design, synthesize, and conduct molecular docking and biological evaluation of pyrido[2,3-d]pyrimidine-2,4(1H,3H)-diones as antibacterial agents.</p><p><strong>Methods: </strong>7-Phenyl-5-(thiophen-2-yl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-diones were designed using an in silico approach. The designed compounds were synthesized using reported procedures. Molecular docking studies were carried out using the Maestro 12.9 module of Schrodinger software. QikProp module of the Schrodinger suite was used for in silico ADME evaluation of synthesized compounds. In vitro antibacterial activity of these compounds was assessed using the serial dilution method.</p><p><strong>Results: </strong>Compounds MA-03 and MA-12 showed potent antibacterial activity with MIC values of 1.56, 3.125, 1.56, and 6.25 μg/ml and 1.56, 3.12, 6.25, and 3.12 μg/ml, respectively, against Bacillus subtilis, Staphylococcus aureus, Pseudomonas putida, and Escherichia coli using controls ciprofloxacin and amoxicillin (0.78, 0.39, 1.56 and 0.39 μg/ml and 0.78, 3.125, 3.125, and 1.56 μg/ml). All the synthesized compounds demonstrated higher binding affinities against bacterial proteins with reference to amoxicillin and ciprofloxacin.</p><p><strong>Conclusion: </strong>All the compounds exhibited antibacterial activity against all the tested strains of bacteria with optimum ADME profile.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181072","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":"Highlighting the Therapeutic Potential of an Underexplored Target: Human Dihydroorotate Dehydrogenase in Cancer, Rheumatoid Arthritis and Sclerosis.","authors":"Shubham Dash, Rupali Verma, Shorya Thakur, Gurvinder Singh, Charanjit Kaur","doi":"10.2174/0115680266359269250521095346","DOIUrl":"https://doi.org/10.2174/0115680266359269250521095346","url":null,"abstract":"<p><strong>Introduction: </strong>The dihydroorotate dehydrogenase (DHODH) enzyme plays a crucial role in the de novo pyrimidine biosynthesis pathway, catalysing the conversion of dihydroorotate to orotate in the cells. This pathway is important for the synthesis of nucleic acids and vital molecules essential for homeostasis, cellular functioning, and survival. So, targeting this enzyme can be an effective approach for the treatment of cancer, arthritis, malaria, viral or microbial infections, and other autoimmune diseases.</p><p><strong>Methods: </strong>In this review, we have highlighted the therapeutic implications of DHODH inhibition in cancer, rheumatoid arthritis and multiple sclerosis through an extensive literature survey from various scientific databases like PubMed, Google Scholar, Science Direct, Embase, clinical trials. gov.in, Google Patents, etc. Results: We have tried to identify the pharmacophores from synthetic, phytochemical, and microbial origins, effective as DHODH inhibitors. The effect of structural changes on activity has been summarised, providing insights into the efficacy and mechanisms of these inhibitors at the molecular level. Furthermore, this review also presents a comprehensive analysis of clinical trials and patents related to DHODH inhibition to extract the valuable information to be used for clinical drug development in cancer, rheumatoid arthritis, and multiple sclerosis.</p><p><strong>Conclusion: </strong>By integrating data from synthetic, plant, and microbial sources, along with clinical trial and patent outcomes, this review highlights the diverse role of DHODH. Its inhibition offers a more targeted approach to reduce the proliferation of rapidly dividing cells while sparing normal cells, modulating specific immune responses. But, limiting understanding of resistance mechanisms and potential for toxicity are the current challenges. It offers a roadmap for future research and drug discovery endeavours focused on harnessing the beneficial potential of DHODH inhibition, including the development of novel inhibitors with improved selectivity and pharmacokinetics across a wide array of pathological conditions.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141650","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":"7-Hydroxyflavone Mitigates Osteoporosis Via Key Signaling Pathways in a Dexamethasone-induced Rat Model.","authors":"Kadirvel Devi, Thukani Sathanantham Shanmugarajan, Velayutham Ravichandiran","doi":"10.2174/0115680266387622250519052501","DOIUrl":"https://doi.org/10.2174/0115680266387622250519052501","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Osteoporosis is a deteriorating skeletal bone disorder that affects in a silent, asymptomatic way. On-demand for new therapeutic strategies, natural products have gained attention as a significant alternative for treating osteoporosis. 7-Hydroxyflavone (7HF) is one of the well-known natural flavones for its anti-inflammatory, anti-oxidant, anti-diabetic, and neuroprotective, which was investigated at the molecular level for restoring bone homeostasis against dexamethasone-induced osteoporosis in vivo with a focus on modulation of oxidative stress (caspase- 3), GATA-3, and NF-kB signaling along with in silico ADMET analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Adult male rats were divided into four groups, containing six in each group. I- Control, II- Dexamethasone (Dexa)-treated disease control, III & IV - 7HF treated group (50, 100mg/kg). Animals in all groups, except the control, were injected with dexamethasone sodium phosphate at the dose level of 7mg/kg, intramuscularly, once a week for five weeks. The third and fourth group animals received 7HF-1 and 7HF-2 as a fine suspension with 2% carboxy methyl cellulose at a dose of 50 and 100mg/kg, respectively, by oral route once daily, starting from the second week of dexamethasone treatment. At the end of the 5th week, blood was collected from the femoral vein after anaesthesia, and the femur bones were dissected. Histopathology, immunohistochemistry of bone, biochemical serum analysis for ALP, TRAP 5b, RANKL, OPG, antioxidants and cytokines, as well as protein expression for RunX2, Bcl2 and Bax were performed. In addition, an analysis of absorption, distribution, metabolism, excretion, and toxicity (ADMET) was conducted for 7HF.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Immunohistochemistry of GATA-3, NF-kB, and caspase-3 on femur bone sections evidenced the suppression of dexamethasone-induced osteoporosis by 7HF. It was found that 7HF lowered the serum levels of cytokines, ALP, TRAP 5b, and RANKL. 7HF elevated the serum level of antioxidants and OPG. In addition, the protein expression of RunX2, and anti-apoptotic Bcl2 was elevated, and the level of pro-apoptotic Bax in rat femur bone tissues was reduced through the use of 7HF. The aforementioned effects of 7HF were more prominent at the dose of 100mg/kg (p&lt;0.001). 7HF exhibited good solubility and efficient absorption in the human intestine, though it showed limited permeability in MDCK cells. It demonstrated positive BBB permeability and Caco- 2 permeability values. 7HF interacted with P-glycoprotein, had an optimal VD, high PPB, and was a substrate and inhibitor of CYP450 enzymes. It functioned effectively as a hERG blocker without inducing human hepatotoxicity. Comprehensive toxicity assessments highlight 7HF as a more suitable option for drug development.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The study data confirmed that concurrent treatment of 7HF showed evident effects in the protection against dexamethasone-induced oste","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141646","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}