Current medicinal chemistry最新文献

{"title":"Medical Artificial Intelligence: Opportunities and Challenges In Infectious Disease Management.","authors":"Ankit Sahoo, Janhvi Singh, Kainat Alam, Nabil K Alruwaili, Alhussain Aodah, Waleed H Almalki, Salem Salman Almujri, Majed Alrobaian, Md Abul Barkat, Tanuja Singh, Jonathan A Lal, Mahfoozur Rahman","doi":"10.2174/0109298673390868250728103906","DOIUrl":"https://doi.org/10.2174/0109298673390868250728103906","url":null,"abstract":"<p><p>Globally, millions of individuals suffer from infectious diseases, which are major public health concerns caused by bacteria, fungi, viruses, or parasites. These diseases can be transmitted directly or indirectly from person to person, potentially leading to a pandemic or epidemic. Several advancements have been made in molecular genetics for infectious disease management, which include pharmaceutical chemistry, medicine, and infection tracking; however, these advancements still lack control over human infections. Multidisciplinary cooperation is needed to address and control human infections. Advancements in scientific tools have empowered scientists to enhance epidemic prediction, gain insights into pathogen specificity, and pinpoint potential targets for drug development. Artificial intelligence (AI)-based methodologies demonstrate significant potential for integrating large-scale quantitative and omics data, enabling effective handling of biological complexity. Machine Learning (ML) plays a crucial role in AI by leveraging data to train predictive models. AI can enhance diagnostic accuracy through objective pattern recognition, standardize infection diagnoses with implications for Infection Prevention and Control (IPC), and aid in generalizing IPC knowledge. Additionally, AIpowered hand hygiene applications have the potential to drive behavioral change, although further evaluation in diverse clinical contexts is necessary. This review article highlights AI's potential in improving the healthcare system in different aspects of infectious diseases management, such as monitoring disease growth, using a real-time chatbot for patient assistance, using image processing for diagnosis, and developing new treatment algorithms. The study also discusses future directions for novel vaccine and drug development, as well as other aspects, such as the need for physicians and healthcare professionals to receive AI system training for their correct use and the ability of doctors to identify and resolve any problems that may arise with AI.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014097","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":"Uridines Modified with Sulfur or Selenium in U-G Wobble Pairs Matter for tRNA Function.","authors":"Katarzyna Kulik, Barbara Nawrot","doi":"10.2174/0109298673367883250716201037","DOIUrl":"https://doi.org/10.2174/0109298673367883250716201037","url":null,"abstract":"<p><p>Transfer RNAs (tRNAs) are ubiquitous in cells and are essential for the translation of genetic information from messenger RNA (mRNA) into proteins in all three domains of life. They act as adaptors that decode mRNA codons via their anticodons and deliver the corresponding amino acids to the growing polypeptide chain. Currently, over 100 modified nucleosides have been found in tRNA that are crucial for the integrity and functionality of this molecule. Almost half of them are located at position 34 of the anticodon, which is commonly referred to as the \"wobble\" position. In this review, we highlight the sulfur- and selenium-modified uridines at this position and discuss their physicochemical properties and regulatory functions in gene expression. We examine how the tRNA anticodons accomplish the decoding of synonymous codons, particularly 5'-NNA- 3' and 5'-NNG-3', and provide efficient uridine -adenosine and uridine - guanosine base pairing. We also analyze the effects of C5 substituents on the tautomeric behavior and ionization properties of 2-thiouridines and 2-selenouridines. Theoretical calculations on the stability of 5-substituted uracil - guanine base pairs and their structural representation in crystal complexes of tRNA-mRNA-ribosomes emphasize the importance of these modifications in fine-tuning translation fidelity and efficiency.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945995","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":"Diverse Development Approaches for Xanthine Oxidase Inhibitors: Synthetic Chemistry, Natural Product Chemistry, and Drug Repositioning.","authors":"Zhihua Xing, Wen Jiang, Yue Xu, Mingyu Gao, Guanghuan Shen, Yingjie Liu, Na Ling, Linlin Cui","doi":"10.2174/0109298673384402250727014932","DOIUrl":"https://doi.org/10.2174/0109298673384402250727014932","url":null,"abstract":"<p><p>Xanthine oxidase (XOD) plays a crucial role in the biosynthesis of uric acid, and inhibiting its activity can effectively reduce the production of uric acid at its source. Currently, clinically used xanthine oxidase inhibitors (XODIs), such as allopurinol and febuxostat, are effective but associated with notable side effects. Allopurinol may induce hypersensitivity reactions, while febuxostat has been reported to potentially increase the risk of severe cardiovascular events. Therefore, the development of Xanthine oxidase inhibitors(XODIs) that lower serum uric acid levels through the inhibition of uric acid production has been a key focus in the research and development of anti-gout medications. This review is based on research literature from 2014 to 2025, sourced from multiple authoritative databases both domestically and internationally, including international databases such as Google Scholar, PubMed, Web of Science, Baidu Scholar, CNKI, Wanfang database. This review systematically summarizes 109 XODIs with urate-lowering or anti-gout pharmacological activities, categorized into chemical synthetic compounds, natural products and their derivatives, and repurposed drugs. The aim is to provide meaningful insights for the development of new therapeutic agents for gout and hyperuricemia. Notably, amides and carboxylic acids among chemically synthesized compounds exhibit promising prospects, while natural products with multiple mechanisms of uric acid reduction hold significant potential for the treatment of hyperuricemia.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946069","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":"Romosozumab's Effect on Bone Mineral Density in Patients with Osteoporosis: A Systematic Review and Meta-Analysis.","authors":"Hooman Yahyazadeh, Tahereh Farkhondeh, Abolfazl Bagherifard, Karo Khosravi, Reza Ahmadi, Hamed Aramjoo, Babak Roshanravan, Saeed Samarghandian","doi":"10.2174/0109298673371957250707161319","DOIUrl":"https://doi.org/10.2174/0109298673371957250707161319","url":null,"abstract":"<p><strong>Introduction: </strong>One of the most effective osteoanabolic drugs for treating osteoporosis is romosozumab, which was developed as a consequence of growing knowledge of the Wnt signaling system. This review explored how romosozumab affects the bone mineral density (BMD) in osteoporotic patients.</p><p><strong>Methods: </strong>Up until January 2024, PubMed, Web of Science, and Scopus were reviewed for any randomized controlled trials (RCTs) evaluating the impact of osteoporotic treatment with romosozumab on BMD changes and bone metabolism markers in primary osteoporosis patients. Pooled Hedges' g indices, which were consistently used across all included studies to measure standardized mean differences, were computed along with their corresponding 95% confidence intervals using either a random-effects or fixed-effects model.</p><p><strong>Results: </strong>Out of the 1855 papers, 24 RCTs met the inclusion criteria. Patients with osteoporosis who received romosozumab for a period of time demonstrated an augmentation in their lumbar spine BMD. The study findings indicated that the total hip and femoral neck BMD demonstrated significant enhancement in 22 (out of 23) and 19 (out of 21) studies, respectively.</p><p><strong>Conclusion: </strong>In patients with osteoporosis, romosozumab could markedly increase the total hip, lumbar spine, and femoral neck BMD. This finding could be verified by measuring bone turnover indicators such as PINP, TRACP-5b, and CTX.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945986","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":"Single-Cell Maps Reveal Novel Mechanisms of Ferroptosis and Biomarkers in Diabetic Nephropathy.","authors":"Yueyi Zhou, Weilin Chen, Dan Li, Li Chen, Bin Yi","doi":"10.2174/0109298673357406250719145527","DOIUrl":"https://doi.org/10.2174/0109298673357406250719145527","url":null,"abstract":"<p><strong>Objective: </strong>Diabetic nephropathy (DN) is the main cause of renal failure due to its complexity and difficulty in prevention. The purpose of our study is to screen potential biomarkers of DN at the single-cell level and reveal its new molecular pathogenesis by single-cell RNA sequencing (scRNA-seq).</p><p><strong>Methods: </strong>In this study, scRNA-seq was performed on kidney tissue of control and DN mice. Through multiple analyses of the data, biomarkers in DN that contribute to early diagnosis were screened, and the complex pathogenesis associated with ferroptosis was revealed and verified by experiments at the animal and cellular levels.</p><p><strong>Results: </strong>Through customized analysis of scRNA-seq results, we found for the first time increased intercellular communication between mesangial epithelial cells and transitional epithelial cells in the pathological state of DN. In addition, two sets of differential protein interaction analysis networks showed that Eno1, Hspa8, FLT1, Hspa1a, and Gsta2 could be used as predictive biomarkers of DN. Finally, the promoting effects of ferroptosis, heat shock protein and their interactions in the development of DN are discussed. In particular, the regulation of GPX4 by members of the heat shock family, Dnaja1 and Hspa1a, promotes lipid peroxidation (the classic phenotype of ferroptosis).</p><p><strong>Conclusion: </strong>In conclusion, we comprehensively analyzed the relevant biomarkers and pathogenesis of DN at single-cell resolution, providing new strategies for therapeutic targets of the disease.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871885","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":"Post-marketing Safety Surveillance of Drug-induced Dementia: Utilizing Signal Detection and Mendelian Randomization in Spontaneous Reports.","authors":"Yan Chen, Chen Li, Yinhui Yao, Yazhen Shang","doi":"10.2174/0109298673378809250707043350","DOIUrl":"https://doi.org/10.2174/0109298673378809250707043350","url":null,"abstract":"<p><strong>Objective: </strong>Many medications associated with an increased risk of dementia do not have adequate warning labels, leading to a significant underestimation of their potential dangers. This study aims to leverage the FAERS database to identify drugs strongly linked to dementia and to examine the relationship between these drugs using Mendelian randomization techniques. The ultimate goal is to mitigate the risk of developing dementia.</p><p><strong>Methods: </strong>We utilized the FAERS database to identify medications significantly associated with dementia cases. The DrugBank, OpenTargets, and STITCH databases were employed to pinpoint the target genes of these drugs. We then conducted Mendelian randomization analysis to explore the correlation between the expression of drug target genes and the incidence of dementia. Additionally, a time-to-onset analysis assessed the temporal relationships of drug ingestions. Furthermore, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction Network (PPI) analyses were performed to investigate the molecular pathways linked to target genes related to drugs associated with dementia.</p><p><strong>Results: </strong>A total of 28,139 dementia events were recorded in the FAERS database. Our Mendelian randomization analysis revealed a significant association between the expression of all identified drug target genes and dementia in both blood and brain tissues. Specifically, we identified nine drug target genes with significant correlations, implicating quetiapine, clozapine, valproic acid, alendronate, and digoxin as being strongly associated with dementia, which could provide insight into areas of clinical concern regarding dementia occurrence.</p><p><strong>Conclusion: </strong>The adverse event data sourced from the FAERS database indicate that certain medications are associated with an increased risk of developing dementia, a finding corroborated by our Mendelian randomization analysis. Establishing a comprehensive monitoring and risk assessment program is crucial for identifying high-risk individuals and facilitating informed medication choices, thereby potentially reducing the incidence of dementia.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871884","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 Comprehensive Analysis of the ITIH Family Across Multiple Cancer Types and an Initial Investigation of ITIH1 in Gastric Cancer.","authors":"Qiangqiang Zhong, Baokang Zhao, Xiao She, Xiangjie Liu","doi":"10.2174/0109298673375809250730142009","DOIUrl":"https://doi.org/10.2174/0109298673375809250730142009","url":null,"abstract":"<p><strong>Introduction: </strong>The ITIH family, crucial for extracellular matrix stability and cancer progression, is underexplored in multi-omic profiles and immune microenvironments; this study analyzes their roles across cancers and ITIH1's function in gastric cancer to reveal diagnostic, prognostic, and therapeutic potential.</p><p><strong>Methods: </strong>We analyzed RNA-seq, protein expr ession, and clinical data from 33 cancer types and 24 non-cancerous conditions using TCGA, GTEx, GEO, CPTAC, and IMvigor210 datasets. Methods included differential expression analysis, ROC curve assessment for diagnostic potential, Cox regression and Kaplan-Meier survival analyses for prognostic value, GSEA for pathway enrichment, and molecular docking for ITIH1-targeted small molecule screening. Immune microenvironment interactions, tumor mutational burden (TMB), microsatellite instability (MSI), and immunotherapy response were evaluated. in vitro experiments validated ITIH1's role in gastric cancer using qRT-PCR, Western blotting, siRNA knockdown, and functional assays.</p><p><strong>Results: </strong>ITIH family genes exhibited differential expression across cancers and non-- cancerous conditions, with ITIH1, ITIH4, and ITIH5 showing high diagnostic potential (AUC > 0.90 in multiple cancers). ITIH1 was a risk factor for poor survival in gastric cancer (p < 0.05). Lower ITIH scores correlated with improved survival in patients receiving immune checkpoint inhibitors (p < 0.05). ITIH genes showed strong correlations with immune checkpoints (PD-1, CTLA-4), TMB, and MSI. Molecular docking identified six small molecules, including Entinostat, with high binding affinity for ITIH1 (-8.4 kcal/mol). ITIH1 knockdown in gastric cancer cell lines (HGC-27, AGS) significantly reduced proliferation, migration, and invasion (p < 0.01).</p><p><strong>Discussion: </strong>This study underscores the ITIH family's critical role as diagnostic and prognostic biomarkers across various cancers and non-cancerous conditions, with ITIH1's therapeutic potential in gastric cancer highlighted through its impact on tumor progression, though limitations include discrepancies in some ITIH gene expressions between in vitro and in vivo settings, necessitating further validation.</p><p><strong>Conclusion: </strong>Our findings highlight the ITIH family's potential as diagnostic biomarkers, prognostic indicators, and therapeutic targets, particularly in gastric cancer. The identification of ITIH1 inhibitors and their association with immune checkpoints, TMB, and MSI paves the way for improved diagnostics, targeted therapies, and immunotherapy predictions, enhancing patient outcomes across diseases.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871882","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":"Investigating the Causal Role of Neurotrophic Factors in Low Back Pain and Sciatica: A Mendelian Randomization Study.","authors":"Feixiang Lin, Wei He","doi":"10.2174/0109298673358689250711005445","DOIUrl":"https://doi.org/10.2174/0109298673358689250711005445","url":null,"abstract":"<p><strong>Background: </strong>Low back pain (LBP) and sciatica are among the most prevalent musculoskeletal disorders, leading to significant disability and an economic burden. Neurotrophic factors, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell-derived neurotrophic factor (GDNF), play critical roles in pain modulation and neuronal function. While NGF-targeting monoclonal antibodies have shown potential in treating chronic pain, their efficacy and safety remain under debate. This study employs Mendelian Randomization (MR) to assess the causal relationships between NGF, BDNF, GDNF, and the risk of LBP and sciatica.</p><p><strong>Methods: </strong>We conducted a two-sample MR analysis using genetic instruments for NGF, BDNF, and GDNF. LBP and sciatica data were obtained from FinnGen. The inverse variance weighted (IVW) method was applied as the primary causal estimation, with the weighted median (WM) and MR-Egger regression used for sensitivity analyses. Reverse MR was performed to evaluate bidirectional causality. Furthermore, we used expression quantitative trait loci (eQTLs) within 50 kb of each gene locus as genetic instruments for NGF regulation, ensuring that the genetic variants used directly influence neurotrophic factor expression.</p><p><strong>Results: </strong>MR analysis revealed a significant causal association between NGF and an increased risk of LBP (OR = 1.121, 95% CI 1.021-1.230, p = 0.016) and sciatica (OR = 1.158, 95% CI 1.034-1.296, p = 0.010), while BDNF and GDNF showed no significant associations with pain outcomes. Sensitivity analyses confirmed the robustness of the NGF findings, with no evidence of horizontal pleiotropy or heterogeneity. Reverse MR analysis showed no significant causal effect of LBP or sciatica on NGF levels (p > 0.05), ruling out reverse causality. Additionally, we investigated the NGF-eQTL, which captures genetically regulated NGF expression, and found a significant association between the NGF-eQTL and LBP (OR = 1.040, 95% CI 1.010-1.070, p = 0.007). Unlike external NGF measurements, the NGF-eQTL minimizes environmental confounding and reverse causation, providing stronger genetic evidence supporting NGF as a therapeutic target for LBP.</p><p><strong>Conclusion: </strong>This study provides genetic evidence that NGF plays a causal role in LBP and sciatica, reinforcing its potential as a therapeutic target. However, BDNF and GDNF were not significantly associated with pain outcomes, suggesting distinct mechanisms of pain modulation. While clinical trials of anti-NGF monoclonal antibodies have demonstrated efficacy in pain reduction, concerns about adverse effects, such as joint degeneration, habe limited their widespread clinical use. Future research should explore genetic predictors of anti-NGF therapy response to optimize treatment strategies for LBP and related musculoskeletal pain disorders.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871883","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 Advanced Network Pharmacology Study Reveals the Multi-Pathway and Multi-Gene Regulatory Mechanism of Jinbai Heat-clearing Prescription in HPV-induced Cervical Cancer via Molecular Docking and Microarray Data Analysis.","authors":"Sui Liu, Zixiao Jiang, Junlei He, Xiangxin Niu, Changhua Yue, Shiou Yih Lee, Zhangxin Yu, Yangyang Liu","doi":"10.2174/0109298673377164250710100915","DOIUrl":"https://doi.org/10.2174/0109298673377164250710100915","url":null,"abstract":"<p><strong>Introduction: </strong>Cervical cancer, primarily driven by high-risk human papillomavirus (HPV) infection, remains a global health challenge due to limited therapeutic efficacy and adverse effects of conventional treatments. Jinbai Heat-Clearing Prescription (JBHCP), a Traditional Chinese Medicine (TCM), exhibits potential against HPV-associated cervical cancer, yet its molecular mechanisms are unclear. This study aimed to elucidate JBHCP's multitarget regulatory mechanisms in HPV-induced cervical carcinogenesis.</p><p><strong>Methods: </strong>Network pharmacology, UHPLC-Q-TOF-MS-based metabolomics, and microarray data analysis were integrated to identify the bioactive components and therapeutic targets of JBHCP. Molecular docking and 60 ns Molecular Dynamics (MD) simulations were used to assess the interactions between key compounds (JBHCP673, JBHCP727) and cyclin-dependent kinases (CDK1/ CDK2). Gene Ontology (GO), KEGG pathway enrichment, and Protein-Protein Interaction (PPI) network analyses were performed to explore biological functions and signaling pathways.</p><p><strong>Results: </strong>UHPLC-Q-TOF-MS identified 816 compounds in JBHCP, with 86 meeting drug-likeness criteria. Network analysis revealed 215 shared targets between JBHCP and HPV-induced cervical cancer, including CDK1 and CDK2 as core regulators. Enrichment analysis highlighted JBHCP's involvement in cell cycle regulation, PI3K/AKT, and STAT3 signaling pathways. Molecular docking demonstrated strong binding affinities of JBHCP727 with CDK1 (-7.36 kcal/mol) and CDK2 (-6.13 kcal/mol). MD simulations confirmed stable binding of JBHCP727 to CDK1/2, while JBHCP673 exhibited instability. ADMET predictions supported JBHCP727's drug-like properties.</p><p><strong>Discussion: </strong>JBHCP exerts anticancer effects by targeting CDK1/2, disrupting cell cycle progression, and modulating oncogenic pathways (PI3K/AKT, STAT3). The stability of JBHCP727-CDK complexes suggests its role in inhibiting HPV-driven proliferation. Multi-component synergy enables JBHCP to act on diverse pathways, aligning with TCM's \"multitarget\" paradigm.</p><p><strong>Conclusion: </strong>This study provides the first systematic evidence of JBHCP's multi-pathway mechanism against HPV-associated cervical cancer, emphasizing CDK1/2 inhibition as a key therapeutic strategy. JBHCP727 emerges as a promising lead compound. Further in vivo and clinical validation is warranted to translate these findings into clinical applications.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834485","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":"Discovery of Furan-tethered Triazolothiadiazoles and Triazolothiadiazines as Potent Tyrosinase Inhibitors for the Treatment of Skin Diseases: Insights from Kinetics Data and Computational Modeling.","authors":"Majid Khan, Atta Ullah, Sobia Ahsan Halim, Imtiaz Khan, Sumera Zaib, Humaira Hussian, Magda H Abdellattif, Afnan Jan, Aliya Ibrar, Ajmal Khan, Ahmed Al-Harrasi","doi":"10.2174/0109298673349818250302105830","DOIUrl":"https://doi.org/10.2174/0109298673349818250302105830","url":null,"abstract":"<p><strong>Introduction: </strong>Tyrosinase, a copper-containing enzyme, is responsible for melanin production, and its overactivity can lead to hyperpigmentation.</p><p><strong>Methods: </strong>This study aimed to evaluate triazolothiadiazoles (3a-h, 4a-f) and triazolothiadiazines (5a-h) against human and mushroom tyrosinase isozymes.</p><p><strong>Results: </strong>Several derivatives, such as 3a-3b, 3d, 4c-4f, 5d, and 5e, were identified as potent and selective inhibitors of mushroom tyrosinase, with IC50 values ranging from 1.9 to 15.2 μM. Similarly, compounds 3f, 4b, 5a, and 5b effectively inhibited human tyrosinase, with IC50 values between 12.6 and 18.5 μM. Mechanism-based studies revealed that these active compounds exhibited competitive inhibition against both isozymes without any cytotoxic effects. In-silico analysis further demonstrated that these compounds fit well into the active site of both tyrosinase isozymes.</p><p><strong>Conclusion: </strong>Additionally, the pharmacokinetic profile of these compounds highlighted promising drug-like properties, making them potential candidates for the development of effective therapeutics for skin disorders.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798469","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}