Current topics in medicinal chemistry最新文献

{"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}

{"title":"Pharmacological Potential of Jasminum auriculatum Extracts Ointment as an Ant Psoriatic Agent: In vivo Evaluation Using Swiss Albino Mice Model.","authors":"Simran Aneja, Neerupma Dhiman, Arun Mittal, Bhupesh Sharma, Rishabha Malviya, Shivam Rajput","doi":"10.2174/0115680266372202250519095446","DOIUrl":"https://doi.org/10.2174/0115680266372202250519095446","url":null,"abstract":"<p><strong>Background: </strong>Synthetic drugs are the drug of choice for topical treatment of psoriasis. However, these are associated with side effects; hence, there is a need to explore effective alternative treatments for psoriasis. Jasminum auriculatum has been used in Ayurvedic and traditional medicine as an ingredient for managing numerous skin ailments like eczema and ringworm.</p><p><strong>Purpose: </strong>This study aimed to evaluate the in vivo study of ointments prepared from chloroform and methanolic extracts of Jasminum auriculatum for the treatment of psoriasis.</p><p><strong>Methods: </strong>Initially, pharmacogenetic and physicochemical characterization of Jasminum auriculatum was performed to check their presence. The ointments prepared from chloroform and methanolic extracts of Jasminum auriculatum were screened for acute toxicity studies and antipsoriatic activity by IMQ-induced psoriasis in the Swiss albino mice ear model. The parameters like ear thickness, ear weight, erythema, scales, and infiltration (Permeation into the skin) were evaluated. The histopathological studies were also conducted to support the findings.</p><p><strong>Results: </strong>The plant showed the presence of pharmacogenetic structures like Trichomes, Palisade cells, Xylem, Collenchyma Tous cells, Parenchymatous cells, Fibers, Pericyclic cells, Stomata, Phloem, and Sclerenchyma Tous cells responsible for the presence of phytoconstituents having antipsoriatic activity. The signs and symptoms increased in imiquimod-induced animals, but ointment of chloroform and methanolic extract of Jasminum auriculatum reduced the skin thickness, redness, scaling, and erythema. The study reveals along with the progression of disease topical formulation of the extract showed the effect on animals in a dose-dependent manner. Histopathological examination also supported the earlier results.</p><p><strong>Conclusions: </strong>The present study demonstrates that ointments of chloroform and methanolic extract of Jasminum auriculatum are safe and effective in the treatment of psoriasis, as revealed by the in vivo study. These preclinical results could further be explored for the development of other topical formulations used in humans.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141571","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":"Structure-Guided Development of Mycobacterial Thymidine Monophosphate Kinase (MtbTMPK) Inhibitors: Unlocking New Frontiers in Tuberculosis Research.","authors":"Suvaiv, Kuldeep Singh, Syed Misbahul Hasan, Shom Prakash Kushwaha, Syed Mehdi Hasan Zaidi, Arun Kumar, Mo Shahanawaz","doi":"10.2174/0115680266372955250514075248","DOIUrl":"https://doi.org/10.2174/0115680266372955250514075248","url":null,"abstract":"<p><p>Researchers are actively engaged in developing new antitubercular drugs targeting the enzyme Mycobacterial Thymidine Monophosphate Kinase (MtTMPK). This newer target has specificity and selectivity over other thymidylate kinases and especially differs from human thymidylate kinase (hTMPK). Over the last two decades, various potent MtTMPK inhibitors comprised of both nucleoside and non-nucleoside structures have been developed. Mostly, nucleoside inhibitors have encountered substantial challenges, primarily related to poor solubility and permeability, which often render them inactive in whole-cell antitubercular assays. Consequently, the focus has shifted towards identifying potent non-nucleoside inhibitors that demonstrate activity in whole-cell assays. Researchers have employed structure-based modifications and leveraged insights from co-crystal structures of Mycobacterium tuberculosis TMPK (MtTMPK) with its natural substrate, thymidine monophosphate (TMP), to develop potent non-nucleoside inhibitors- such as cynopyridone and 5-methylpyridine analogues-which have demonstrated nanomolar enzyme inhibitory activity. However, the problem was persistent and only a few non-nucleoside inhibitors have been found to be active in whole-cell activity, likewise nucleoside inhibitors. The reason behind the uncertainty between enzyme inhibitory and whole cell antitubercular activity of developed inhibitors remains incomprehensible to date, even though the efflux pump and permeability- related studies have been performed. Despite numerous efforts, no antitubercular drug targeting MtTMPK has reached the market or clinical trials, though some non-nucleoside inhibitors are in preclinical stages. As MtTMPK is crucial for Mycobacterium tuberculosis survival and its inhibition effectively reduces the growth of the bacteria, making it a promising target for novel antitubercular drugs. In addition to thymidine-like core structures, several inhibitors with non-thymidine-like cores have also been developed as potent MtTMPK inhibitors, opening new opportunities for future research to explore the uncharted chemical space of this target.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141574","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":"MHA-SVR: An Adaptive Soft Sensor Based on Feature Interaction for Ultrasonic Phytomedicine Extraction.","authors":"Yuqi Yue, Zepeng Xue, Zhongyu Guo, Juan Chen","doi":"10.2174/0115680266356325250510064641","DOIUrl":"https://doi.org/10.2174/0115680266356325250510064641","url":null,"abstract":"<p><strong>Introduction: </strong>Ultrasonic extraction is a crucial technique for isolating active compounds from phytomedicine. However, as a batch process characterized by non-linearity and small sample size, it poses substantial challenges for real-time and prediction of extraction rates during the extraction of phytomedicinal. This work proposes an adaptive soft sensor for ultrasonic phytomedicine extraction.</p><p><strong>Method: </strong>An adaptive soft sensor based on an attention mechanism was first proposed. The attention mechanism calculates correlations between samples and assigns weights based on their similarity to the current query. Support vector regression (SVR) is then used to construct the soft sensor for extraction rate measurement. To further enhance sample information analysis, multi-head attention is employed. This allows the model to calculate the similarity between current queries and historical data across different feature spaces, thus improving the modeling capabilities of the intrinsic data structure. Finally, a dual-frequency ultrasonic extraction experiment of puerarin is designed and conducted. The experimental data is collected and labeled from different batches under varying initial extraction temperatures. This data is used to establish the soft sensor model and compare its performance.</p><p><strong>Results and discussion: </strong>The experimental results indicate that the proposed MHA-SVR model improved the coefficient of determination (R²) by 5.12% compared to the mainstream model and reduced the online prediction time by 88% compared to the JITL-SVR model. This work performance well exceeds the others while maintaining good real-time capabilities for the dual-frequency ultrasonic extraction of puerarin.</p><p><strong>Conclusion: </strong>The multi-head attention and SVR-integrated soft sensor method proposed in this study effectively addresses the soft measurement challenges in online monitoring of multi-batch ultrasonic extraction processes. This approach demonstrates significant enhancement in extraction yield detection accuracy across varying batches and diverse initial operating conditions, thereby providing a robust technical solution for real-time quantification of extraction efficiency in botanical material processing.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110058","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":"Targeting Cell Signalling Pathways with New Small Molecules in Inflammation and Cancer.","authors":"Ritam Mondal, Kalpana Rahate, Sandhya Chaudhary","doi":"10.2174/0115680266360926250509040743","DOIUrl":"https://doi.org/10.2174/0115680266360926250509040743","url":null,"abstract":"<p><p>In the treatment of cancer and inflammation, small molecules become powerful therapeutic tools that provide new therapeutic approaches with improved efficacy and fewer side effects. This review offers a thorough summary of current developments in small-molecule drugs that target cancer and inflammatory pathways. Specifically, inhibition of phosphodiesterase-4 (PDE4) and COX receptors have demonstrated potential in the field of inflammation to help mitigate a variety of inflammatory disorders. We examine the structural design, mechanism of action, and therapeutic potential of innovative small compounds that inhibit or alter these pathways. Significant attention is placed on the dual anti-inflammatory and anti-cancer properties of these substances. The evaluation emphasizes preclinical and clinical data, revealing the most promising candidates under development. In summary, the precise manipulation of cellular signalling pathways by small compounds constitutes a dynamic domain with the capacity to revolutionize therapeutic approaches for inflammation and cancer. Ongoing investigation of these chemicals is essential for the advancement of safer and more efficacious therapies.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983241","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":"Traditional Chinese Medicines for Alzheimer's Disease: Current Knowledge, Clinical Applications, and Future Directions.","authors":"Yu Deng, Chaojun Chen, Hongtao Li, Tianle Wang, Xu Zhang, Xueyang Wang, Guangtao Pan","doi":"10.2174/0115680266347052250407110353","DOIUrl":"https://doi.org/10.2174/0115680266347052250407110353","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a prevalent neurodegenerative disorder that poses a significant challenge to the health of the global aging population. Despite extensive research, the complex mechanisms underlying AD pathogenesis remain largely elusive. In recent years, a growing number of clinical studies have demonstrated the preventive and therapeutic potential of Traditional Chinese Medicine (TCM) against AD through multiple pathways, targets, and compounds. In this study, we conducted a review of the literature published over the past 20 years through international and domestic databases, including PubMed, Medline, Cochrane Library, CNKI, SinoMed, Wanfang, and VIP Journal Integration Platform. This review systematically evaluates current research advancements regarding single-herb preparations, bioactive constituents, and compound formulations in Traditional Chinese Medicine (TCM), with focused analysis on three therapeutic categories: tonifying herbs, blood-activating and stasis-eliminating agents, as well as orifice-opening, phlegm-resolving, and mind-stabilizing medicinal substances. Furthermore, this review discusses the potential mechanisms underpinning the anti-AD effects of TCMs. By integrating these insights, this review aims to establish a theoretical foundation for the application of TCMs in AD treatment and provide a reference for future pharmacological studies and the development of health-related products.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985087","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 MMP1 Inhibitors from Dandelion using Molecular Simulation and Bioactivity Test.","authors":"Yaxuan Huang, Dewen Jiang, Liqin Zhang, Yonghao Zhang, Mingkai Wu, Xiaojie Jin, Jianjun Luo, Dabo Pan","doi":"10.2174/0115680266387669250509094221","DOIUrl":"https://doi.org/10.2174/0115680266387669250509094221","url":null,"abstract":"<p><strong>Background: </strong>MMP1 (matrix metallopeptidase 1) plays a significant role in the degradation of collagen fibres within the extracellular matrix, and has been linked to a multitude of biological processes, including rheumatoid arthritis, osteoarthritis, periodontal disease, and tumor invasion.</p><p><strong>Objective: </strong>In order to discover inhibitors of MMP1 that originate from the phytochemicals of the dandelion (Taraxacum mongolicum Hand.-Mazz.).</p><p><strong>Methods: </strong>The herbal constituents of the dandelion were retrieved from the HERB database. A multifaceted approach including molecular docking, MMP1 enzyme assays, and molecular dynamics simulations was used to identify potential MMP1 inhibitors among the chemical compounds present in the dandelion.</p><p><strong>Results: </strong>A total of 61 chemical constituents of the dandelion were collated from the HERB database. A potential MMP1 inhibitor was identified through a combination of molecular docking and an MMP1 enzyme bioactivity assay. Cichoric acid demonstrated pronounced inhibitory activity against MMP1, with an IC50 value of 7.81 ± 2.60 µM. Molecular dynamics simulations and binding free energy calculations indicated that the nonpolar interaction energies of LEU181, ARG214, VAL215, HIS218, GLU219, HIS228, PRO238, and SER239 played a primary role in the binding of cichoric acid to MMP1.</p><p><strong>Conclusion: </strong>The integration of molecular modeling and bioactivity testing proved an effective method for the rapid discovery of targeted small molecule inhibitors. Cichoric acid demonstrated potent MMP1 inhibitory activity and thus represented a promising candidate for further development.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978985","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":"Integrative Analysis Reveals Genes Causal Relation with Ovarian Cancer and aging.","authors":"Lanhui Qin, Chongze Yang, Rui Song, Pei-Yin Chen, Zijian Jiang, Weihui Xu, Guanzhen Zeng, Jin-Yuan Liao, Liling Long","doi":"10.2174/0115680266358687250507041056","DOIUrl":"https://doi.org/10.2174/0115680266358687250507041056","url":null,"abstract":"<p><strong>Background: </strong>Exploring the correlation between ovarian cancer and aging has great significance for understanding the pathogenesis of ovarian cancer and formulating targeted therapeutic regimens.</p><p><strong>Objective: </strong>This computational study aims to identify and validate key genes in monocyte subtypes related to ovarian cancer and aging, exploring potential causal relationships.</p><p><strong>Method: </strong>We collected single-cell RNA sequencing data (GSE157007, GSE184880), GWAS data (14,049 samples and 40,941 controls from a European population), and eQTL data of ovarian cancer and aging. Using R software packages like Seurat and singleR, we conducted data integration, quality control, cell classification, and differential gene expression analysis to identify intersecting monocyte subtype genes in ovarian cancer and aging. We employed summary data-based Mendelian randomization (SMR) analysis and Heterogeneity in Dependent Instruments (HEIDI) tests to pinpoint causal genes. Further single-cell functional analyses (gene switching, cell communication, metabolic pathway analysis), Bulk RNA sequencing validation, functional enrichment, and protein- protein interaction (PPI) analyses elucidated these genes' biological roles.</p><p><strong>Results: </strong>The dataset included 123,280 cells, revealing differential gene expression in classical monocytes (104 genes), intermediate monocytes (43 genes), and myeloid dendritic cells (39 genes). SMR and HEIDI identified causal relationships for 7 genes in classical monocytes, 3 in intermediate monocytes, and 3 in myeloid dendritic cells with ovarian cancer. Bulk RNA seq validation confirmed six monocyte genes as causal in ovarian cancer and aging. TREM1, SERPINB2, and CD44 were upregulated, while DST was downregulated; SLC11A1 and PNRC1 showed contradictory patterns. Interactions with NK and T cells involved LGALS9 - CD44/45 receptors. Riboflavin metabolism was a common enriched pathway.</p><p><strong>Conclusion: </strong>This study identified six specific monocyte genes as potential therapeutic targets for ovarian cancer and aging.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989835","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}