Chemical Biology & Drug Design最新文献

{"title":"Tyramine Derivatives as Versatile Pharmacophores With Potent Biological Properties: Sex Hormone–Binding Globulin Inhibition, Colon Cancer Antimigration, and Antimicrobial Activity","authors":"Jovana S. Marjanović,&nbsp;Dejan Arsenijević,&nbsp;Marijana Kosanić,&nbsp;Jovana Matić,&nbsp;Goran A. Bogdanović,&nbsp;Marina D. Kostić,&nbsp;Vera M. Divac","doi":"10.1111/cbdd.70001","DOIUrl":"https://doi.org/10.1111/cbdd.70001","url":null,"abstract":"<div>\u0000 \u0000 <p>Guided by the idea that the presence of a heterocyclic aromatic core and tyramine moiety, under the umbrella of a single molecular scaffold could bring interesting biological properties, herein we present synthesis, characterization, with two crystal structures reported, and biological evaluation of some tyramine derivates. Cytotoxic and antimigratory potential was addressed by using a colorectal cancer cell line as a model system. Although possessing no cytotoxic effects, two compounds have shown strong antimigratory potential in low doses, with no effect on healthy MRC-5 cells. Evaluation of their antimicrobial activities suggested prominent antimicrobial activity, where Compound <b>4</b> outperformed streptomycin against <i>Escherichia coli</i> and <i>Proteus mirabilis</i>. Hormone-dependent types of cancer, such as prostate, ovary, and breast, are highly dependent on human sex hormone–binding globulin (SHBG) blood levels. A molecular docking study has shown that <b>1</b> has high affinity to bind and therefore compete with natural steroids for the SHBG steroid-binding site. DNA-binding study have shown that <b>4</b> interacts with CT-DNA in a groove-binding mode. <i>In silico</i> ADME/T study revealed that all compounds have suitable physicochemical properties for oral bioavailability and druglikeness, while toxicity tests for <b>1</b>, <b>4,</b> and <b>6</b> suggested potential for mutagenicity (<b>4, 6</b>), hepatotoxicity (<b>6</b>), and skin sensation (<b>1</b>).</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443414","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":"Apelin-13's Actions in Controlling Hypertension-Related Cardiac Hypertrophy and the Expressions of Inflammatory Cytokines","authors":"Xiaoliang Wei,&nbsp;Liyun Luo,&nbsp;Huifang Lu,&nbsp;Songbiao Li,&nbsp;Xinlian Deng,&nbsp;Zhihui Li,&nbsp;Dong Gong,&nbsp;Bairong Chen","doi":"10.1111/cbdd.14628","DOIUrl":"https://doi.org/10.1111/cbdd.14628","url":null,"abstract":"<div>\u0000 \u0000 <p>As a key molecule for improving cardiovascular diseases, Apelin-13 was surveyed in this work to explain its actions in controlling inflammation, pyroptosis, and myocardial hypertrophy. First, mouse models with myocardial hypertrophy were established. Then, assessments were made on the pathological variation in the heart of mouse, on the cardiac functions, as well as on the expressions of cardiac hypertrophy markers (β-MHC, ANP, and BNP), inflammatory factors (TNF-α, COX2, IL-6, ICAM-1, and VCAM-1), myocardial cell pyroptosis markers (NLRP3, ASC, c-caspase-1, and GSDMD-N), and Hippo pathway proteins (p-YAP, YAP, LATS1, and p-LATS1) by HE staining, echocardiography scanning, and western blot tests separately. The expressions of such inflammatory factors as in myocardial tissue were acquired by ELISA. After inducing the phenotype of H9c2 cell hypertrophy by noradrenaline, we used CCK-8 kits to know about the activity of H9c2 cells treated with Apelin-13, and performed ɑ-actinin staining to measure the changes in volumes of such cells. As unraveled through this work, Apelin-13 refrained the activation of the Hippo pathway, which in turn attenuated the hypertrophy, inflammation, and pyroptosis of myocardial tissue and H9c2 cells. Hence, Apelin-13 can be considered as a target for hypertension treatment.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435358","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":"Anti-metastatic Effects of Bee Venom and Melittin in Breast Cancer Cells by Upregulation of BRMS1 and DRG1 Genes","authors":"Nur Sena Sivri,&nbsp;Sinan Tetikoğlu,&nbsp;Sevgi Kolayli,&nbsp;Ammad Ahmad Farooqi,&nbsp;Selcen Çelik Uzuner","doi":"10.1111/cbdd.14637","DOIUrl":"https://doi.org/10.1111/cbdd.14637","url":null,"abstract":"<div>\u0000 \u0000 <p>Apitherapy has started to gain tremendous recognition because of extraordinary pharmacological importance of honeybee-related ingredients and their derivatives. There has been a renewed interest in the bee venom–based therapies. Interdisciplinary researchers are studying the chemistry and translational value of venom for effective cancer treatment. Bee venom and its major component, melittin, are cytotoxic in cancer cells. In this study, MTT and scratch assays were performed for analysis of melittin-mediated antimetastatic effects. QPCR was used for expression profiling of metastasis-related genes. Three anti-metastatic genes (<i>BRMS1</i>, <i>DRG1</i>, and <i>KAI1</i>/<i>CD82</i>) were studied for the first time after bee venom and melittin treatment in MDA-MB-231 breast cancer cells compared with normal breast cells, and two prometastatic genes (<i>EGFR</i> and <i>WNT7B</i>) were also examined. KAI1/CD82 and BRMS1 are the negative regulators of EGFR. WNT7B is a negative regulator of KAI1/CD82. Selective cytotoxicity of bee venom and melittin was found to be higher as compared to cisplatin. Melittin induced an increase in the expression of BRMS1 and DRG1, whereas bee venom upregulated DRG1 and KAI1/CD82 expression in breast cancer. <i>WNT7B</i> was downregulated in bee venom–treated breast cancer cells. Results suggested that bee venom/melittin exerted antimetastatic effects primarily through upregulation of <i>BRMS1</i>, <i>DRG1</i>, and <i>KAI1</i>/<i>CD82</i>, and downregulation of <i>WNT7B</i>.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435359","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 Artificial Intelligence and Its Impact in Pharmaceutical Sciences: Insights Toward the Horizons Where Technology Meets Tradition","authors":"Shruti Bharadwaj,&nbsp;Kumari Deepika,&nbsp;Asim Kumar,&nbsp;Shivani Jaiswal,&nbsp;Shaweta Miglani,&nbsp;Damini Singh,&nbsp;Prachi Fartyal,&nbsp;Roshan Kumar,&nbsp;Shareen Singh,&nbsp;Mahendra Pratap Singh,&nbsp;Abhay M. Gaidhane,&nbsp;Bhupinder Kumar,&nbsp;Vibhu Jha","doi":"10.1111/cbdd.14639","DOIUrl":"https://doi.org/10.1111/cbdd.14639","url":null,"abstract":"<p>The technological revolutions in computers and the advancement of high-throughput screening technologies have driven the application of artificial intelligence (AI) for faster discovery of drug molecules with more efficiency, and cost-friendly finding of hit or lead molecules. The ability of software and network frameworks to interpret molecular structures' representations and establish relationships/correlations has enabled various research teams to develop numerous AI platforms for identifying new lead molecules or discovering new targets for already established drug molecules. The prediction of biological activity, ADME properties, and toxicity parameters in early stages have reduced the chances of failure and associated costs in later clinical stages, which was observed at a high rate in the tedious, expensive, and laborious drug discovery process. This review focuses on the different AI and machine learning (ML) techniques with their applications mainly focused on the pharmaceutical industry. The applications of AI frameworks in the identification of molecular target, hit identification/hit-to-lead optimization, analyzing drug–receptor interactions, drug repurposing, polypharmacology, synthetic accessibility, clinical trial design, and pharmaceutical developments are discussed in detail. We have also compiled the details of various startups in AI in this field. This review will provide a comprehensive analysis and outline various state-of-the-art AI/ML techniques to the readers with their framework applications. This review also highlights the challenges in this field, which need to be addressed for further success in pharmaceutical applications.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.14639","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational Insights Into the Mechanism of EGCG's Binding and Inhibition of the TDP-43 Aggregation","authors":"Vini D. Meshram,&nbsp;Ramkumar Balaji,&nbsp;Preethi Saravanan,&nbsp;Yashashwini Subbamanda,&nbsp;Waghela Deeksha,&nbsp;Akarsh Bajpai,&nbsp;Himanshu Joshi,&nbsp;Anamika Bhargava,&nbsp;Basant K. Patel","doi":"10.1111/cbdd.14640","DOIUrl":"10.1111/cbdd.14640","url":null,"abstract":"<div>\u0000 \u0000 <p>Misfolding and aggregation of TAR DNA-binding protein, TDP-43, is linked to devastating proteinopathies such as ALS. Therefore, targeting TDP-43's aggregation is significant for therapeutics. Recently, green tea polyphenol, EGCG, was observed to promote non-toxic TDP-43 oligomer formation disallowing TDP-43 aggregation. Here, we investigated if the anti-aggregation effect of EGCG is mediated via EGCG's binding to TDP-43. In silico molecular docking and molecular dynamics (MD) simulation suggest a strong binding of EGCG with TDP-43's aggregation-prone C-terminal domain (CTD). Three replicas, each having 800 ns MD simulation of the EGCG-TDP-43-CTD complex, yielded a high negative binding free energy (Δ<i>G</i>) inferring a stable complex formation. Simulation snapshots show that EGCG forms close and long-lasting contacts with TDP-43's Phe-313 and Ala-341 residues, which were previously identified for monomer recruitment in CTD's aggregation. Notably, stable physical interactions between TDP-43 and EGCG were also detected in vitro using TTC staining and isothermal titration calorimetry which revealed a high-affinity binding site of EGCG on TDP-43 (<i>K</i>_d, 7.8 μM; Δ<i>G</i>, −6.9 kcal/mol). Additionally, TDP-43 co-incubated with EGCG was non-cytotoxic when added to HEK293 cells. In summary, EGCG's binding to TDP-43 and blocking of residues important for aggregation can be a possible mechanism of its anti-aggregation effects on TDP-43.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395962","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 Advances in Medicinal Chemistry of Memantine Against Alzheimer's Disease","authors":"Yash Pal Singh,&nbsp;Harish Kumar","doi":"10.1111/cbdd.14638","DOIUrl":"10.1111/cbdd.14638","url":null,"abstract":"<div>\u0000 \u0000 <p>Alzheimer's disease (AD) is a chronic progressive, age-related neurodegenerative brain disorder characterized by the irreversible decline of memory and other cognitive functions. It is one of the major health threat of the 21st century, which affects around 60% of the population over the age of 60 years. The problem of this disease is even more major because the existing pharmacotherapies only provide symptomatic relief without addressing the basic factors of the disease. It is characterized by the extracellular deposition of amyloid β (Aβ) to form senile plaques, and the intracellular hyperphosphorylation of tau to form neurofibrillary tangles (NFTs). Due to the complex pathophysiology of this disease, various hypotheses have been proposed, including the cholinergic, Aβ, tau, oxidative stress, and the metal–ion hypothesis. Among these, the cholinergic and Aβ hypotheses are the primary targets for addressing AD. Therefore, continuous advances have been made in developing potential cholinesterase inhibitors and <i>N</i>-methyl-D-aspartate (NMDA) receptor antagonists to delay disease progression and restore cholinergic neurotransmission. In this review article, we tried to comprehensively summarize the recent advancement in NMDA receptor antagonist (memantine) and their hybrid analogs as potential disease-modifying agents for the treatment of AD. Furthermore, we also depicted the design, rationale, and SAR analysis of the memantine-based hybrids used in the last decade for the treatment of AD.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382760","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":"Evaluation of Quinoline-Related Carboxylic Acid Derivatives as Prospective Differentially Antiproliferative, Antioxidative, and Anti-Inflammatory Agents","authors":"Shereen Arabiyat,&nbsp;Ahmad Alzoubi,&nbsp;Hala Al-Daghistani,&nbsp;Yusuf Al-Hiari,&nbsp;Violet Kasabri,&nbsp;Rema Alkhateeb","doi":"10.1111/cbdd.14615","DOIUrl":"10.1111/cbdd.14615","url":null,"abstract":"<div>\u0000 \u0000 <p>The higher prevalence of cancer and the unmet need for antioxidant/anti-inflammatory chemotherapeutic compounds with little side effect are of utmost importance. In addition, the increased likelihood of failure in clinical trials along with increasing development costs may have diminished the range of choices among newer drugs for clinical use. This has dictated the necessity to seek out novel medications by repurposing as it needs less time, effort, and resources to explore new uses of a current or unsuccessful medication. In this study, we examined the biological activity of 10 potential quinoline derivatives. Given the half-maximal inhibitory concentration (IC₅₀ value) in lipopolysaccharide (LPS) induced inflammation of RAW264.7 mouse macrophages, all commercial FQs and selected quinolines (quinoline-4-carboxlic and quinoline-3-carboxylic acids) exerted impressively appreciable anti-inflammation affinities versus classical NSAID indomethacin without related cytotoxicities in inflamed macrophages. Conversely, all 14 tested compounds lacked antioxidative DPPH radical scavenging capacities as compared to ascorbic acid. Gemifloxacin, considerably unlike markets FQs, indomethacin and quinoline derivatives, exerted exceptional and differential antiproliferation propensities in colorectum SW480, HCT116, and CACO2, pancreatic PANC1, prostate PC3, mammary T47D, lung A375, and melanoma A549 adherent monolayers using the sulforhodamine B colorimetric method versus antineoplastic cisplatin. All quinoline derivatives and gemifloxacin alike, but not levofloxacin, ciprofloxacin, or indomethacin, displayed substantially selective viability reduction affinities in prolonged tumor incubations of cervical HELA and mammary MCF7 cells. Specifically kynurenic acid (hydrate), quinoline-2-carboxylic acid, quinoline-4-carboxylic acid, quinoline-3-carboxylic acid, and 1,2-dihydro-2-oxo-4-quinoline carboxylic acids possessed the most remarkable growth inhibition capacities against mammary MCF7 cell line, while quinoline-2-carboxylic acid was the only quinoline derivative with significant cytotoxicity on cervical HELA cancer cells. It is highly speculated that chelation with divalent metals via co-planarity with close proximity of the COOH and the N atom could have the potential molecular mechanism for optimally promising repurposed pharmacologies. Conclusively, this study revealed the considerably profound repurposed duality of cytotoxicity and anti-inflammation pharmacologies of quinoline derivatives. Activity-guided structural modifications of the present nuclear scaffolds can be inherently linked to the betterment and enhancement of their repurposed pharmacologies.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367867","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":"Comment on “Integrative Analysis of Ex Vivo Studies and Microarray Reveals the Novel Inhibitor Effects of Trehalose on the Pathogenesis of Pterygium”","authors":"Thiago Gonçalves dos Santos Martins","doi":"10.1111/cbdd.14636","DOIUrl":"10.1111/cbdd.14636","url":null,"abstract":"","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334360","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":"Synthesis, Antioxidant Activity, and Molecular Docking of Novel Paeoniflorin Derivatives","authors":"Jiating Ni,&nbsp;Meng Yang,&nbsp;Xinyue Zheng,&nbsp;Mingtao Wang,&nbsp;Qian Xiao,&nbsp;Hua Han,&nbsp;Peiliang Dong","doi":"10.1111/cbdd.14629","DOIUrl":"https://doi.org/10.1111/cbdd.14629","url":null,"abstract":"<div>\u0000 \u0000 <p>Paeoniflorin (PF) is one of the active constituents of the traditional Chinese medicine <i>Paeoniae Radix</i> Rubra and has been actively explored in the pharmaceutical area due to its numerous pharmacological effects. However, severe difficulties such as limited bioavailability and low permeability limit its utilization. Therefore, this study developed and synthesized 25 derivatives of PF, characterized them by ¹H NMR, ¹³C NMR, and HR-MS, and evaluated their antioxidant activity. Firstly, the antioxidant capacity of PF derivatives was investigated through DPPH radical scavenging experiment, ABTS radical scavenging experiment, reducing ability experiment, and O₂^.− radical scavenging experiment. PC12 cells are routinely used to evaluate the antioxidant activity of medicines, therefore we utilize it to establish a cellular model of oxidative stress. Among all derivatives, compound 22 demonstrates high DPPH radical scavenging capacity, ABTS radical scavenging ability, reduction ability, and O₂^.− radical scavenging ability. The results of cell tests reveal that compound 22 has a non-toxic effect on PC12 cells and a protective effect on H₂O₂-induced oxidative stress models. This might be due to the introduction of 2, 5-difluorobenzene sulfonate group in PF, which helps in scavenging free radicals under oxidative stress. Western blot and molecular docking indicated that compound 22 may exert antioxidant activity by activating Nrf2 protein expression. As noted in the study, compound 22 has the potential to be a novel antioxidant.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142324674","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":"Dehydroepiandrosterone-α-2-Deoxyglucoside Exhibits Enhanced Anticancer Effects in MCF-7 Breast Cancer Cells and Inhibits Glucose-6-Phosphate Dehydrogenase Activity","authors":"Hsu-Feng Liu,&nbsp;Shen-Chieh Chou,&nbsp;Sheng-Cih Huang,&nbsp;Tzu-Yu Huang,&nbsp;Po-Yun Hsiao,&nbsp;Feng-Pai Chou,&nbsp;Tung-Kung Wu","doi":"10.1111/cbdd.14624","DOIUrl":"https://doi.org/10.1111/cbdd.14624","url":null,"abstract":"<p>In the pentose phosphate pathway, dehydroepiandrosterone (DHEA) uncompetitively inhibits glucose-6-phosphate dehydrogenase (G6PD), reducing NADPH production and increasing oxidative stress, which can influence the onset and/or progression of several diseases, including cancer. 2-Deoxy-D-glucose (2-DG), a glucose mimetic, competes with glucose for cellular uptake, inhibiting glycolysis and competing with glucose-6-phosphate (G-6-P) for G6PD activity. In this study, we report that DHEA-α-2-DG (<b>5</b>), an α-covalent conjugate of DHEA and 2-DG, exhibits better anticancer activity than DHEA, 2-DG, DHEA +2-DG, and polydatin in MCF-7 cells, and reduces NADPH/NADP⁺ ratio in cellular assays. In vitro enzyme kinetics and molecular docking studies showed that <b>5</b> uncompetitively inhibits human G6PD activity and binds to the structural NADP⁺ site but not to the catalytic NADP⁺ site. Further combining <b>5</b> with the FDA-approved drug tamoxifen enhanced its cytotoxicity against MCF-7 cells, suggesting that it could serve as a candidate for combination of drug strategies.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.14624","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142316891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}