Journal of Enzyme Inhibition and Medicinal Chemistry最新文献_第3页

Rational design, synthesis, and molecular modelling insights of dual DNA binders/DHFR inhibitors bearing arylidene-hydrazinyl-1,3-thiazole scaffold with apoptotic and anti-migratory potential in breast MCF-7 cancer cells. 具有乳腺癌MCF-7细胞凋亡和抗迁移潜力的芳基烯-肼基-1,3-噻唑支架双DNA结合物/DHFR抑制剂的合理设计、合成和分子建模见解

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-03-04 DOI: 10.1080/14756366.2025.2468353

Marwa H El-Wakil, Rasha A Ghazala, Hadeel A El-Dershaby, Danuta Drozdowska, Agnieszka Wróbel-Tałałaj, Cezary Parzych, Artur Ratkiewicz, Beata Kolesińska, Heba A Abd El-Razik, Farid S G Soliman

{"title":"Rational design, synthesis, and molecular modelling insights of dual DNA binders/DHFR inhibitors bearing arylidene-hydrazinyl-1,3-thiazole scaffold with apoptotic and anti-migratory potential in breast MCF-7 cancer cells.","authors":"Marwa H El-Wakil, Rasha A Ghazala, Hadeel A El-Dershaby, Danuta Drozdowska, Agnieszka Wróbel-Tałałaj, Cezary Parzych, Artur Ratkiewicz, Beata Kolesińska, Heba A Abd El-Razik, Farid S G Soliman","doi":"10.1080/14756366.2025.2468353","DOIUrl":"10.1080/14756366.2025.2468353","url":null,"abstract":"In light of searching for new breast cancer therapies, DNA-targeted small molecules were rationally designed to simultaneously bind DNA and inhibit human dihydrofolate reductase (hDHFR). Fourteen new arylidene-hydrazinyl-1,3-thiazoles (5-18) were synthesised and their dual DNA groove binding potential and in vitro hDHFR inhibition were performed. Two compounds, 5 and 11, proved their dual efficacy. Molecular docking and molecular dynamics simulations were performed for those active derivatives to explore their mode of binding and stability of interactions inside DHFR active site. Anti-breast cancer activity was assessed for 5 and 11 on MCF-7 cells using MTX as reference. IC50 measurements revealed that both compounds were more potent and selective than MTX. Cytotoxicity was examined against normal skin fibroblasts to examine safety and selectivity Moreover, mechanistic studies including apoptosis induction and wound healing were performed. Further in silico ADMET assessment was conducted to determine their eligibility as drug leads suitable for future optimisation and development.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2468353"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Discovery of a novel PLK1 inhibitor with high inhibitory potency using a combined virtual screening strategy. 使用联合虚拟筛选策略发现一种具有高抑制效力的新型PLK1抑制剂。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-03-07 DOI: 10.1080/14756366.2025.2467798

Zhen Xu, Lixia Guan, Yuting Wang, Miao-Miao Niu, Yashi Ruan, Cen Xu, Li Yang

引用次数: 0

27-Hydroxycholesterol in cancer development and drug resistance. 27-羟基胆固醇在癌症发展和耐药中的作用。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-05-22 DOI: 10.1080/14756366.2025.2507670

Yaxin Hou, Zhiguang Fu, Chenhui Wang, Paulina Kucharzewska, Yuan Guo, Sihe Zhang

{"title":"27-Hydroxycholesterol in cancer development and drug resistance.","authors":"Yaxin Hou, Zhiguang Fu, Chenhui Wang, Paulina Kucharzewska, Yuan Guo, Sihe Zhang","doi":"10.1080/14756366.2025.2507670","DOIUrl":"10.1080/14756366.2025.2507670","url":null,"abstract":"27-Hydroxycholesterol (27HC), a cholesterol metabolite, functions both as a selective oestrogen receptor (ER) modulator and a ligand for liver X receptors (LXRs). The discovery of 27HC involvement in carcinogenesis has unveiled new research avenues, yet its precise role remains controversial and context-dependent. In this review, we provide an overview of the biosynthesis and metabolism of 27HC and explore its cancer-associated signalling, with a particular focus on ER- and LXR-mediated pathways. Given the tissue-specific dual role of 27HC, we discuss its differential impact across various cancer types. Furthermore, we sort out 27HC-contributed drug resistance mechanisms from the perspectives of drug efflux, cellular proliferation, apoptosis, epithelial-mesenchymal transition (EMT), antioxidant defence, epigenetic modification, and metabolic reprogramming. Finally, we highlight the chemical inhibitors to mitigate 27HC-driven cancer progression and drug resistance. This review offers an updated role of 27HC in cancer biology, setting the stage for future research and the development of targeted therapeutics.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2507670"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of potent inhibitors of potential VEGFR2: a graph neural network-based virtual screening and in vitro study. 潜在VEGFR2的有效抑制剂的鉴定：基于图神经网络的虚拟筛选和体外研究。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-06-20 DOI: 10.1080/14756366.2025.2518192

Shengzhen Hou, Shuning Diao, Yuxiang He, Taiying Li, Wenhui Meng, Jinping Zhang

{"title":"Identification of potent inhibitors of potential VEGFR2: a graph neural network-based virtual screening and in vitro study.","authors":"Shengzhen Hou, Shuning Diao, Yuxiang He, Taiying Li, Wenhui Meng, Jinping Zhang","doi":"10.1080/14756366.2025.2518192","DOIUrl":"10.1080/14756366.2025.2518192","url":null,"abstract":"VEGFR2 is a transmembrane tyrosine kinase receptor expressed on vascular endothelial cells and is closely associated with tumour cell growth. A comparison of traditional Chinese medicines and natural products with existing VEGFR2 inhibitors revealed that the former exhibited superior anticancer properties while concomitantly showing a reduced incidence of adverse effects. We proposed a novel strategy for screening potential candidates targeting VEGFR2 in a Chinese medicine monomer database using a combination of AI deep learning and structure-based drug design. The graph neural network served as the final predictive model to evaluate the molecular activities within the database, resulting in the selection of six candidate compounds. Kinase inhibition assays showed that the three compounds exhibited significant inhibition of VEGFR2. Molecular docking and molecular dynamics simulations further demonstrated the stability of their binding to VEGFR2. This study identified three compounds that effectively inhibited VEGFR2, making them promising candidates in cancer treatment.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2518192"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Medicinal chemistry breakthroughs on ATM, ATR, and DNA-PK inhibitors as prospective cancer therapeutics. ATM， ATR和DNA-PK抑制剂作为前瞻性癌症治疗药物的药物化学突破。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-04-21 DOI: 10.1080/14756366.2025.2489720

Ram Sharma, Anshul Mishra, Monika Bhardwaj, Gurpreet Singh, Larasati Vanya Indira Harahap, Sakshi Vanjani, Chun Hsu Pan, Kunal Nepali

{"title":"Medicinal chemistry breakthroughs on ATM, ATR, and DNA-PK inhibitors as prospective cancer therapeutics.","authors":"Ram Sharma, Anshul Mishra, Monika Bhardwaj, Gurpreet Singh, Larasati Vanya Indira Harahap, Sakshi Vanjani, Chun Hsu Pan, Kunal Nepali","doi":"10.1080/14756366.2025.2489720","DOIUrl":"https://doi.org/10.1080/14756366.2025.2489720","url":null,"abstract":"This review discusses the critical roles of Ataxia Telangiectasia Mutated Kinase (ATM), ATM and Rad3-related Kinase (ATR), and DNA-dependent protein kinase (DNA-PK) in the DNA damage response (DDR) and their implications in cancer. Emphasis is placed on the intricate interplay between these kinases, highlighting their collaborative and distinct roles in maintaining genomic integrity and promoting tumour development under dysregulated conditions. Furthermore, the review covers ongoing clinical trials, patent literature, and medicinal chemistry campaigns on ATM/ATR/DNA-PK inhibitors as antitumor agents. Notably, the medicinal chemistry campaigns employed robust drug design strategies and aimed at assembling new structural templates with amplified DDR kinase inhibitory ability, as well as outwitting the pharmacokinetic liabilities of the existing DDR kinase inhibitors. Given the success attained through such endeavours, the clinical pipeline of DNA repair kinase inhibitors is anticipated to be supplemented by a reasonable number of tractable entries (DDR kinase inhibitors) soon.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2489720"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pyridine indole hybrids as novel potent CYP17A1 inhibitors. 吡啶吲哚杂化物作为新型有效的CYP17A1抑制剂。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-02-14 DOI: 10.1080/14756366.2025.2463014

Tomasz M Wróbel, Angelika Grudzińska, Jibira Yakubu, Therina du Toit, Katyayani Sharma, Jeremiah C Harrington, Fredrik Björkling, Flemming Steen Jørgensen, Amit V Pandey

{"title":"Pyridine indole hybrids as novel potent CYP17A1 inhibitors.","authors":"Tomasz M Wróbel, Angelika Grudzińska, Jibira Yakubu, Therina du Toit, Katyayani Sharma, Jeremiah C Harrington, Fredrik Björkling, Flemming Steen Jørgensen, Amit V Pandey","doi":"10.1080/14756366.2025.2463014","DOIUrl":"10.1080/14756366.2025.2463014","url":null,"abstract":"Prostate cancer (PCa) is one of the most prevalent malignancies affecting men worldwide, and androgen deprivation therapy (ADT) is a primary treatment approach. CYP17A1 inhibitors like abiraterone target the steroidogenic pathway to reduce androgen levels, but their clinical efficacy is limited by drug resistance and adverse effects. This study reports the synthesis and evaluation of novel CYP17A1 inhibitors derived from a previously identified hit compound. Several analogs were synthesised, including an unexpected di-cyano derivative, which demonstrated increased potency against CYP17A1 compared to abiraterone. Biological assays revealed that these compounds significantly inhibited CYP17A1 enzymatic activity and altered steroid biosynthesis. Among the newly synthesised inhibitors, compound 11 showed the highest potency (IC50 = 4 nM) and the related compound 14 presented a template for further development. A combined docking and molecular dynamics approach was used to identify the possible target binding modes of the compounds.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2463014"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Design, synthesis and biological activity of novel Xuetongsu derivatives as potential anticancer agents by inducing apoptosis. 新型血通素衍生物诱导细胞凋亡的设计、合成及生物活性研究。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-04-08 DOI: 10.1080/14756366.2025.2482140

Qi Jiang, Hui Zhong, Cong Wu, Jia Li, Jingmin Chen, Xudong Zhou, Bin Li, Huanghe Yu, Wei Wang, Wenbing Sheng

{"title":"Design, synthesis and biological activity of novel Xuetongsu derivatives as potential anticancer agents by inducing apoptosis.","authors":"Qi Jiang, Hui Zhong, Cong Wu, Jia Li, Jingmin Chen, Xudong Zhou, Bin Li, Huanghe Yu, Wei Wang, Wenbing Sheng","doi":"10.1080/14756366.2025.2482140","DOIUrl":"10.1080/14756366.2025.2482140","url":null,"abstract":"Xuetongsu (XTS, Schisanlactone E) is one of the main active compounds and considered as the star molecule isolated from Kadsura heteroclita (Roxb.) Craib. In order to improve XTS anti-tumour bioactivities, a series of novel XTS derivatives were designed and synthesised by introducing an amide bond at the parent. Anti-proliferative assays on four different human tumour cell lines (BGC-823, HepG-2, HCT-116, and MCF-7) showed that the anti-tumour activities of most derivatives increased greatly compared to the parent XTS, and especially, compounds A-7, A-14, and A-18 exhibited multiple anti-tumour effects. Among them, compound A-7 has the best biological activities on the four tumour cell lines with the IC50 values ranging from 13.86 to 20.71 μM, which could significantly increase the fraction of apoptotic cells according to flow cytometry experience. Further study demonstrated that A-7 could induce apoptosis on HepG-2 cells through influencing the key apoptotic related proteins, such as Bcl-2, Bax, and cleaved Caspase-3.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2482140"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural isomerisation affects the antitubercular activity of adamantyl-isoxyl adducts. 结构异构化影响金刚烷基异氧基加合物的抗结核活性。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-05-21 DOI: 10.1080/14756366.2025.2502600

Yucheng Lu, Daniel Partleton, Filibus M Gugu, Ahmed Y G Alhejaili, Samuel Norris, J Jonathan Harburn, Jason H Gill, Jonathan D Sellars, Alistair K Brown

{"title":"Structural isomerisation affects the antitubercular activity of adamantyl-isoxyl adducts.","authors":"Yucheng Lu, Daniel Partleton, Filibus M Gugu, Ahmed Y G Alhejaili, Samuel Norris, J Jonathan Harburn, Jason H Gill, Jonathan D Sellars, Alistair K Brown","doi":"10.1080/14756366.2025.2502600","DOIUrl":"10.1080/14756366.2025.2502600","url":null,"abstract":"Despite efforts to discover effective treatments to eradicate tuberculosis (TB), it remains a global threat. The increase in drug-resistant bacterial species has made the discovery of new drugs highly coveted. The utilisation of previous efficacious structures is one approach that can be employed to developing novel series of compounds to combat this ever-growing problem. This study sought to re-examine two such compounds, isoxyl (ISO) and SQ109, previously shown to be efficacious in TB treatment. SQ109-ISO hybrid compounds were shown to have demonstrable activity against both drug-sensitive and drug-resistant Mtb whilst displaying limited toxicity in vitro in comparison to other antitubercular agents. Indications from our genetic and biochemical studies suggest that these structurally similar pharmacophores bind to different proteins within Mtb, highlighting the need for careful consideration when producing regioisomeric analogues and that the utilisation of previous efficacious structures is a valid approach to developing promising novel drugs against Mtb.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2502600"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Design and synthesis of 1,4,8-triazaspiro[4.5]decan-2-one derivatives as novel mitochondrial permeability transition pore inhibitors. 新型线粒体通透性过渡孔抑制剂1,4,8-三氮杂螺[4.5]癸烷-2- 1衍生物的设计与合成。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-05-21 DOI: 10.1080/14756366.2025.2505907

Valentina Albanese, Gaia Pedriali, Martina Fabbri, Antonella Ciancetta, Silvia Ravagli, Chiara Roccatello, Remo Guerrini, Giampaolo Morciano, Delia Preti, Paolo Pinton, Salvatore Pacifico

{"title":"Design and synthesis of 1,4,8-triazaspiro[4.5]decan-2-one derivatives as novel mitochondrial permeability transition pore inhibitors.","authors":"Valentina Albanese, Gaia Pedriali, Martina Fabbri, Antonella Ciancetta, Silvia Ravagli, Chiara Roccatello, Remo Guerrini, Giampaolo Morciano, Delia Preti, Paolo Pinton, Salvatore Pacifico","doi":"10.1080/14756366.2025.2505907","DOIUrl":"10.1080/14756366.2025.2505907","url":null,"abstract":"Ischaemia/reperfusion injury (IRI) is a condition that occurs when tissues from different organs undergo reperfusion following an ischaemic event. The mitochondrial permeability transition pore (mPTP), a multiprotein platform including structural components of ATP synthase with putative gate function, is an emerging pharmacological target that could be modulated to facilitate the restoration of organ function after a hypoxic insult. Herein, we reported the synthesis and biological characterisation of new molecules with a 1,4,8-triaza-spiro[4.5]decan-2-one framework of potential interest for the treatment of IRI able to inhibit the opening of mPTP in a cardiac model in vitro. Modelling studies were useful to rationalise the observed structure-activity relationship detecting a binding site for the investigated molecules at the interface between the c8-ring and subunit a of ATP synthase. Compound 14e was shown to display high potency as mPTP inhibitor combined with the capability to counteract cardiomyocytes death in an in vitro model of hypoxia/reoxygenation.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2505907"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Study on the synthesis and biological activity of kojic acid triazol thiosemicarbazide Schiff base derivatives. 曲酸三唑硫代氨基脲席夫碱衍生物的合成及生物活性研究。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-04-08 DOI: 10.1080/14756366.2025.2475071

Yayuan Luo, Zhiyong Peng, Junyuan Tang, Dahan Wang, Sheng Tao, Jinbing Liu

{"title":"Study on the synthesis and biological activity of kojic acid triazol thiosemicarbazide Schiff base derivatives.","authors":"Yayuan Luo, Zhiyong Peng, Junyuan Tang, Dahan Wang, Sheng Tao, Jinbing Liu","doi":"10.1080/14756366.2025.2475071","DOIUrl":"10.1080/14756366.2025.2475071","url":null,"abstract":"A series of kojic acid triazol thiosemicarbazide Schiff base derivatives were designed and synthesised. Evaluation on the inhibition of tyrosinase activity showed that these compounds possessed potent inhibit tyrosinase activity, and the compound 6w (IC50 = 0.94 μM) exhibited the best inhibitory effect. Preliminary structure-activity relationships indicate that steric hindrance, halogen atom radius, and electron donating ability of functional groups have some impact on the inhibition of tyrosinase activity. Inhibition mechanism showed that compound 6w is a non-competitive mixed inhibitor, and this result was further confirmed by molecular docking. The fluorescence quenching mode of compound 6w is dynamic quenching, and interacts with tyrosinase by changing the amide structure of tyrosinase. Compound 6w has some anti-browning effect. Compound 6p had the strongest DPPH radical scavenging activity (IC50 = 10.53 ± 0.014 μM), and compound 6w showed the best ABTS scavenging activity (IC50 = 3.03 ± 0.009 μM).","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2475071"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0