Journal of Enzyme Inhibition and Medicinal Chemistry最新文献_第5页

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

Design, synthesis, and bioevaluation of pyrazole-containing tubulin polymerisation inhibitors based on conformational constraint strategy. 基于构象约束策略的含吡唑微管蛋白聚合抑制剂的设计、合成和生物评价。

IF 5.4 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-09-23 DOI: 10.1080/14756366.2025.2545004

Zhongqiao Sun, Jiahao Wang, Fengwei Li, Liancheng Huang, Shide Zheng, Qi Guan, Zhaohua Wang, Weige Zhang

{"title":"Design, synthesis, and bioevaluation of pyrazole-containing tubulin polymerisation inhibitors based on conformational constraint strategy.","authors":"Zhongqiao Sun, Jiahao Wang, Fengwei Li, Liancheng Huang, Shide Zheng, Qi Guan, Zhaohua Wang, Weige Zhang","doi":"10.1080/14756366.2025.2545004","DOIUrl":"10.1080/14756366.2025.2545004","url":null,"abstract":"Based on conformational preference of SMART analogues and conformational constraint strategy, two series of new tubulin polymerisation inhibitors (4a - 4k and 5a - 5h/6a - 6h) were designed via hydrogen bonding, steric effect (for 4a - 4k) and ring-closing approach by fused five- and seven-membered ring (for 5a - 5h/6a - 6h) which was first adopted in the design of new SMART analogues. Among these compounds, 4k and 5a showed potent activities with IC50 values of 15 nM and 6 nM against PC-3 cell line. Mechanism studies indicated that 4k and 5a could inhibit tubulin polymerisation, arrest cell cycle at G2/M phase, induce cell apoptosis, and inhibit cell migration and colony formation. Molecular docking suggested that compounds 4k and 5a could bind into the colchicine binding site at the pose similar to DAMA-colchicine. Western blot assays revealed that 4k and 5a regulated the expression of cell cycle and apoptosis-related proteins. Prediction of physicochemical properties indicated good drug-likeness of 4k and 5a.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2545004"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12459184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124410","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

Green ultrasound‑assisted deep eutectic solvent extraction of flavonoid enzyme inhibitors from Blumea aromatica: process optimization, characterization, and mechanistic insights into α‑glucosidase and tyrosinase inhibition. 绿色超声辅助下的深共晶溶剂萃取蓝花中黄酮类酶抑制剂：工艺优化、表征以及α -葡萄糖苷酶和酪氨酸酶抑制的机理研究。

IF 5.4 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-09-04 DOI: 10.1080/14756366.2025.2552445

Wei Dai, Liping Dai, Tao Su, Qin Lin, Zhiwen Lin, Shuxin Ye, Peihao Xu, Hongfeng Chen, Xilong Zheng

{"title":"Green ultrasound‑assisted deep eutectic solvent extraction of flavonoid enzyme inhibitors from Blumea aromatica: process optimization, characterization, and mechanistic insights into α‑glucosidase and tyrosinase inhibition.","authors":"Wei Dai, Liping Dai, Tao Su, Qin Lin, Zhiwen Lin, Shuxin Ye, Peihao Xu, Hongfeng Chen, Xilong Zheng","doi":"10.1080/14756366.2025.2552445","DOIUrl":"10.1080/14756366.2025.2552445","url":null,"abstract":"A green ultrasound-assisted deep eutectic solvent (UAE-DES) method was optimised for extracting flavonoid enzyme inhibitors from Blumea aromatica. Optimal conditions (choline chloride-1,4-butanediol 1:3 molar ratio, 43% water content, 50 mL/g liquid-to-solid ratio, 80 °C ultrasound for 48 min) yielded 3.15% total flavonoids, 45.2% higher than 50% ethanol extraction. Scanning electron microscopy confirmed cell wall disruption. The UAE-DES extract showed the strongest enzyme inhibition among all extracts tested (IC50 35.872 ± 0.294 µg/mL for α-glucosidase, 9.126 ± 0.285 μg/mL for tyrosinase), though the α-glucosidase inhibition was much weaker than acarbose, while tyrosinase inhibition was comparable to kojic acid. Six flavonoids were identified via UPLC-Q-Orbitrap HRMS, including scutellarein and corylin. Molecular docking revealed strong binding affinities (≤ -5 kcal/mol), with corylin showing the highest binding to both enzymes through hydrogen bonds and van der Waals interactions. This approach supports sustainable discovery of natural enzyme inhibitors for antidiabetic and skin-whitening applications.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2552445"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12412317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992741","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

Ligand-based discovery of novel N-arylpyrrole derivatives as broad-spectrum antimicrobial agents with antibiofilm and anti-virulence activity. 基于配体的新型n -芳基吡咯衍生物作为具有抗生物膜和抗毒活性的广谱抗菌药物的发现。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-07-08 DOI: 10.1080/14756366.2025.2523970

Basma M Qandeel, Samar Mowafy, Mohamed F El-Badawy, Nahla A Farag, Galal Yahya, Khaled Abouzid

{"title":"Ligand-based discovery of novel N-arylpyrrole derivatives as broad-spectrum antimicrobial agents with antibiofilm and anti-virulence activity.","authors":"Basma M Qandeel, Samar Mowafy, Mohamed F El-Badawy, Nahla A Farag, Galal Yahya, Khaled Abouzid","doi":"10.1080/14756366.2025.2523970","DOIUrl":"10.1080/14756366.2025.2523970","url":null,"abstract":"The escalating threat of antimicrobial resistance calls for novel therapeutic agents. This study employed a ligand-based design approach to develop three series of N-arylpyrrole derivatives (Va-e, VIa-e, and VIIa-e), refined through molecular modeling. Synthesized compounds were evaluated against ESKAPE pathogens, MRSA, and Mycobacterium phlei. Series Va-e showed the most promise, with compounds Vb, Vc, and Ve outperforming levofloxacin against MRSA (MIC = 4 μg/mL vs. 8 μg/mL). Vc also exhibited activity against E. coli, K. pneumoniae, and A. baumannii, and showed significant inhibition against M. phlei (MIC = 8 μg/mL). Compounds were evaluated for antibiofilm and antivirulence properties, targeting resistance mechanisms linked to infection persistence and dissemination. Most exhibited broad-spectrum biofilm inhibition and antivirulence activity. Cytotoxicity studies revealed selectivity for bacterial cells. ADMET studies supported drug-like properties. Docking studies suggested UPPP inhibition as the potential mechanism. SAR analysis was conducted to support future optimizations.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2523970"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584083","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

Correction. 修正。

IF 5.4 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-07-28 DOI: 10.1080/14756366.2025.2537523

引用次数: 0

Development of triaryl antimicrobials by scaffold hopping from an aminopropanol hit targeting bacterial RNA polymerase-NusG interactions. 利用氨基丙醇撞击靶向细菌RNA聚合酶nusg相互作用的支架跳变制备三芳基抗菌剂。

IF 5.4 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-08-18 DOI: 10.1080/14756366.2025.2543923

Tiankuang Liu, Cheuk Hei Kan, Yingbo Zheng, Tsz Fung Tsang, Yanpeng Liu, Man Wai Tsang, Hantian Fang, Long Yin Lam, Xiao Yang, Cong Ma

{"title":"Development of triaryl antimicrobials by scaffold hopping from an aminopropanol hit targeting bacterial RNA polymerase-NusG interactions.","authors":"Tiankuang Liu, Cheuk Hei Kan, Yingbo Zheng, Tsz Fung Tsang, Yanpeng Liu, Man Wai Tsang, Hantian Fang, Long Yin Lam, Xiao Yang, Cong Ma","doi":"10.1080/14756366.2025.2543923","DOIUrl":"10.1080/14756366.2025.2543923","url":null,"abstract":"Bacterial RNA polymerase (RNAP) requires the NusG factor to facilitate transcription, with the RNAP clamp-helix domain (CH) serving as the primary binding site for NusG and representing a promising target for antimicrobial intervention. In previous work, we unprecedentedly developed a pharmacophore model based on key clamp-helix residues (R270, R278, R281) at RNAP CH essential for NusG binding, which led to the identification of a hit compound exhibiting modest antimicrobial activity against Streptococcus pneumoniae. In this study, we designed a new class of triaryl inhibitors via scaffold hopping, substituting the linear structure of the hit compound with a benzene ring. Antimicrobial testing showed that several newly synthesised lead compounds achieved the minimum inhibitory concentration of 1 µg/mL against drug-resistant S. pneumoniae, superior to some marketed antibiotics. The following inhibitory and cell-based assays demonstrated the potential of these triaryl compounds as promising candidates for further development as novel antimicrobial agents.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2543923"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12364105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873483","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