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

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

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

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

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

A stable GH31 α-glucosidase as a model system for the study of mutations leading to human glycogen storage disease type II. 稳定的GH31 α-葡萄糖苷酶作为研究人类糖原储存病II型突变的模型系统。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-02-24 DOI: 10.1080/14756366.2025.2468859

Roberta Iacono, Francesca Maria Pia Paragliola, Andrea Strazzulli, Marco Moracci

{"title":"A stable GH31 α-glucosidase as a model system for the study of mutations leading to human glycogen storage disease type II.","authors":"Roberta Iacono, Francesca Maria Pia Paragliola, Andrea Strazzulli, Marco Moracci","doi":"10.1080/14756366.2025.2468859","DOIUrl":"10.1080/14756366.2025.2468859","url":null,"abstract":"GH31 glycosidases are widespread across organisms, but remarkably, less than 1% of them have been biochemically characterised to date. Among them, human lysosomal acid α-glucosidase (GAA) stands out due to its link to Pompe disease, a rare lysosomal storage disorder caused by its deficiency. This disease results in glycogen accumulation, severe cellular damage, motor impairment, and premature death. Structural and functional studies of GAA mutants are challenging due to their instability and lack of activity, hindering their expression and purification. The GH31 enzyme MalA from a hyperthermophilic archaeon is explored here as a stable homolog of GAA. MalA is highly expressible, easy to purify, and structurally characterised. The R400H mutant in MalA, corresponding to the pathogenic GAA R600H mutation, revealed here a 1200-fold drop in specificity constant and >8 °C reduction in thermal stability. We propose MalA's as a robust model for studying GAA mutations and developing therapeutic chaperones.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2468859"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492356","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 a novel and high affinity MIF inhibitor via structure-based pharmacophore modelling, molecular docking, molecular dynamics simulations, and biological evaluation. 通过基于结构的药效团模型、分子对接、分子动力学模拟和生物学评价鉴定一种新型高亲和力MIF抑制剂。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-06-15 DOI: 10.1080/14756366.2025.2501378

Shang Zhu, Shudan Yang, Yao Chen, Miao-Miao Niu, Jun Wang, Jindong Li, Xuehua Pu

{"title":"Identification of a novel and high affinity MIF inhibitor via structure-based pharmacophore modelling, molecular docking, molecular dynamics simulations, and biological evaluation.","authors":"Shang Zhu, Shudan Yang, Yao Chen, Miao-Miao Niu, Jun Wang, Jindong Li, Xuehua Pu","doi":"10.1080/14756366.2025.2501378","DOIUrl":"10.1080/14756366.2025.2501378","url":null,"abstract":"Macrophage migration inhibitory factor (MIF) plays a crucial role in disrupting immune homeostasis and was overexpressed in immune cells. The inhibitors of MIF inhibit the release of inflammatory factors to treat sepsis. Herein, a series of compounds (termed as Hits 1-6) were discovered based on pharmacophore modelling, molecular docking, and interaction analysis. The biaryltriazole inhibitor 3a was used as the positive control. MST and ITC experiments showed that compared to 3a, Hit-1 possessed the highest affinity with MIF. MD simulations exhibited that Hit-1 stably bound to the active pocket of MIF. Pull down experiment showed that Hit-1 could interfere with the binding of MIF to CD74. Furthermore, RT-qPCR demonstrated that Hit-1 suppressed the release of pro-inflammatory cytokines in macrophages including TNF-α, IL-6, and IL-1β. These data demonstrate that Hit-1 may be a promising and high-affinity candidate compound treating sepsis.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2501378"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302230","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

Unlocking the potential of trifluoromethyl pyrrole derivatives in chronic wounds management: rapid synthesis, structural insights, and potent antimicrobial activity. 释放三氟甲基吡咯衍生物在慢性伤口管理中的潜力：快速合成，结构见解和有效的抗菌活性。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-06-11 DOI: 10.1080/14756366.2025.2513406

Rafaela Vrabie, Mariana Pinteala, Cristina M Al-Matarneh, Ioana C Marinas, Alina Nicolescu, Sergiu Shova, Mihaela Silion, Mădălina-Diana Gaboreanu, Mariana C Chifiriuc

{"title":"Unlocking the potential of trifluoromethyl pyrrole derivatives in chronic wounds management: rapid synthesis, structural insights, and potent antimicrobial activity.","authors":"Rafaela Vrabie, Mariana Pinteala, Cristina M Al-Matarneh, Ioana C Marinas, Alina Nicolescu, Sergiu Shova, Mihaela Silion, Mădălina-Diana Gaboreanu, Mariana C Chifiriuc","doi":"10.1080/14756366.2025.2513406","DOIUrl":"10.1080/14756366.2025.2513406","url":null,"abstract":"Using a one-pot, three-component approach, we synthesised 25 dihydropyrrol-2-one and two 5-oxo-2,5-dihydrofuran compounds, each featuring two trifluoromethyl groups. This method emphasises timeliness and cost-effectiveness, crucial in drug development. Structural verification was conducted using NMR, FT-IR, MALDI-MS, single-crystal, and powder XRD. The antibacterial and antifungal activities of these compounds were evaluated on yeasts (Candida sp.) and bacteria, including Gram-positive (Staphylococcus aureus, a significant opportunistic pathogen, being more susceptible than S. epidermidis) and Gram-negative strains. Compounds with o-OH and m'-NO2 groups exhibited superior activity, while those with p-OH and m-OMe groups showed slightly lower but still significant activity. For furan structures, Candida albicans displayed greater sensitivity than C. parapsilosis. Additionally, 13 compounds demonstrated haemolysis below 5%, indicating low toxicity.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2513406"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266397","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

Hidden targets in dermatology: In vitro and In silico inhibitory effects of common 23 dermatologic drugs on human carbonic anhydrase isoenzymes I and II. 皮肤病学中的隐藏靶点：23种常见皮肤药物对人碳酸酐酶同工酶I和II的体外和体内抑制作用

IF 5.4 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-08-05 DOI: 10.1080/14756366.2025.2540935

İlkay Can, Kübra Çıkrıkcı, Nahit Gençer, Harun Uslu

{"title":"Hidden targets in dermatology: In vitro and In silico inhibitory effects of common 23 dermatologic drugs on human carbonic anhydrase isoenzymes I and II.","authors":"İlkay Can, Kübra Çıkrıkcı, Nahit Gençer, Harun Uslu","doi":"10.1080/14756366.2025.2540935","DOIUrl":"10.1080/14756366.2025.2540935","url":null,"abstract":"In this study, we have aimed to determine the in vitro and in silico effects of 23 frequently used dermatologic drugs on human carbonic anhydrase I (hCA I) and II (hCA II). The inhibitory effects of the drugs on hCA I and hCA II were determined by esterase methods. The most potent inhibitors were isotretinoin for hCA I (Ki= 5.75 µM) and valaciclovir for hCA II (Ki= 5.74 µM). Ketotifen (Ki= 6.98 µM), pantoprazole (Ki= 7.16 µM) and acyclovir (Ki= 7.31 µM) were also potent inhibitors for hCA I. Isotretinoin (Ki= 6.54 µM), brivudine (Ki= 7.44 µM) and fluconazole (Ki= 7.91 µM) were also potent inhibitors for hCA II. Terbinafine hydrochloride was a weak CA inhibitor for both of these isoenzymes (Ki= 20.58 µM for hCA I and 20.32 µM for hCA I). Therefore, the drug, having a weak CA inhibitory activity, may be preferred primarily in patients with a skin disease compared to the other drugs due to important physiological functions of CAs. Molecular docking studies have shown that acitretin and isotretinoin, in particular, will inhibit hCA I at lower concentrations and have higher docking scores. For hCA II, it was shown that Isotretinoin and Ketotifen would inhibit at lower concentrations and have higher placement scores.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2540935"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12326379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784410","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