Journal of Enzyme Inhibition and Medicinal Chemistry最新文献_第9页

Discovery and development of steroidal enzyme inhibitors as anti-cancer drugs: state-of-the-art and future perspectives. 甾体酶抑制剂作为抗癌药物的发现和发展：最新进展和未来展望。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-04-02 DOI: 10.1080/14756366.2025.2483818

Bruno Cerra, Antimo Gioiello

{"title":"Discovery and development of steroidal enzyme inhibitors as anti-cancer drugs: state-of-the-art and future perspectives.","authors":"Bruno Cerra, Antimo Gioiello","doi":"10.1080/14756366.2025.2483818","DOIUrl":"10.1080/14756366.2025.2483818","url":null,"abstract":"Steroidal compounds have emerged as effective therapeutic agents in oncology. Beyond natural-occurring and synthetic steroids that act as cytotoxic anti-tumoral agents, steroidal derivatives can be designed to mime the endogenous substrates of key metabolic enzymes in steroidogenesis, thus reducing the circulating levels of relevant oestrogenic and androgenic hormones responsible for cancer survival and proliferation. Therefore, enzyme inhibition represents an intriguing endocrine approach for the treatment of hormone-dependent tumours, such as breast and prostate cancer, with well-known approved drugs and several pre-clinical and clinical candidates under investigation. This review summarises the key advancements over the past decade (2014-2024) in the development of steroidal enzyme inhibitors endowed with anticancer activity, illustrating their mechanisms of action, therapeutic potential, drug design approaches, and current clinical applications. Furthermore, we discuss challenges related to drug resistance, off-target effects, and future strategies to optimise their efficacy in oncology.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2483818"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11967001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764180","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

Structure-based design of new potent and highly selective PARP-1 inhibitor for treating colorectal cancer. 基于结构的新型高效、高选择性PARP-1抑制剂治疗结直肠癌的设计。

IF 5.4 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-08-12 DOI: 10.1080/14756366.2025.2542358

Chunying Jiang, Shudan Yang, Yuting Wang, Liyuan Du, Miao-Miao Niu, Dongli Zhang

引用次数: 0

Exploring structure-activity relationships of pyrrolyl diketo acid derivatives as non-nucleoside inhibitors of terminal deoxynucleotidyl transferase enzyme. 探讨吡咯酰二酮酸衍生物作为末端脱氧核苷酸转移酶非核苷类抑制剂的构效关系。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-06-09 DOI: 10.1080/14756366.2025.2496782

Valentina Noemi Madia, Nadia Garibaldi, Davide Ialongo, Elisa Patacchini, Valeria Tudino, Giuseppe Ruggieri, Laura Zarbo, Emanuele Cara, Antonio Coluccia, Marco Artico, Luigi Scipione, Antonella Messore, Francesco Saccoliti, Elisa Mentegari, Giovanni Maga, Roberto Di Santo, Emmanuele Crespan, Roberta Costi

{"title":"Exploring structure-activity relationships of pyrrolyl diketo acid derivatives as non-nucleoside inhibitors of terminal deoxynucleotidyl transferase enzyme.","authors":"Valentina Noemi Madia, Nadia Garibaldi, Davide Ialongo, Elisa Patacchini, Valeria Tudino, Giuseppe Ruggieri, Laura Zarbo, Emanuele Cara, Antonio Coluccia, Marco Artico, Luigi Scipione, Antonella Messore, Francesco Saccoliti, Elisa Mentegari, Giovanni Maga, Roberto Di Santo, Emmanuele Crespan, Roberta Costi","doi":"10.1080/14756366.2025.2496782","DOIUrl":"10.1080/14756366.2025.2496782","url":null,"abstract":"Terminal deoxynucleotidyl transferase (TdT) is overexpressed in some cancer types, where it drives the mutagenic repair of double strand breaks through non canonical non-homologous end joining pathway. The TdT enzyme belongs to the X family of polymerases, together with the DNA polymerase λ (pol λ) and β (pol β). However, TdT exclusively displays template-independent nucleotide polymerisation. Pursuing our studies in developing TdT inhibitors, herein we deepened the structure-activity relationships of new structural analogues of our previously identified hit compounds. The diketo hexenoic acid derivatives here analysed showed high selectivity towards TdT and inhibition potencies spanning from the low micromolar range to the nanomolar. Docking studies highlighted the chemical features involved in the TdT binding, well contributing to the rationalisation of the structural requirements needed for the enzymatic inhibition.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2496782"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248222","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

Site-selective arylations of nature-inspired flavonoids or steroidal phenols via C-H or O-H activation. 通过C-H或O-H活化的天然类黄酮或甾体酚的位点选择性芳基化。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-07-18 DOI: 10.1080/14756366.2025.2530615

Rebeka Ignácz, Noémi Bózsity, Dénes Unger, Zoltán Kele, István Zupkó, Attila Hunyadi, Marija Gjorgoska, Tea Lanišnik Rižner, Erzsébet Mernyák

{"title":"Site-selective arylations of nature-inspired flavonoids or steroidal phenols via C-H or O-H activation.","authors":"Rebeka Ignácz, Noémi Bózsity, Dénes Unger, Zoltán Kele, István Zupkó, Attila Hunyadi, Marija Gjorgoska, Tea Lanišnik Rižner, Erzsébet Mernyák","doi":"10.1080/14756366.2025.2530615","DOIUrl":"10.1080/14756366.2025.2530615","url":null,"abstract":"Phenols are important structural elements of natural products and pharmaceuticals. Due to their versatile chemical transformability, phenols are frequently used building blocks in medicinal chemistry. Their aromatic nature allows directed C(sp2)-H functionalisations, especially at the ortho positions. In contrast, meta substitutions are less well known. As a continuation of our recently described metal-catalysed cross couplings, here we report arylations of two nature-inspired phenol derivatives via C-H or O-H activation. A directing group (DG) was introduced onto C-3-O of 13α-oestrone, and the resulting carbamate was subjected to Cu(II)-catalysed meta arylation using diaryliodonium triflates as reagents. As a result, C-1-arylated derivatives were obtained. The arylation of the 1'-O-butyl protoapigenone proceeded regioselectively at C-5-O. The 1-(4-tert-butylphenyl)-13α-oestrone carbamate and all O-arylated protoflavones substantially inhibited the growth of the applied human cancer cell lines and exerted proapoptotic activity on HeLa cells. The 1-(4-tert-butylphenyl)-13α-oestrone proved to be a potent 17β-HSD1 inhibitor.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2530615"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659379","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

Inhibition mechanism and behaviour of wedelolactone against α-glucosidase. 魏德内酯对α-葡萄糖苷酶的抑制机制及行为。

IF 5.4 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-09-02 DOI: 10.1080/14756366.2025.2551970

Jianjun Zhang, Min Zhao, Fan Wu, Zheng Shi, Rui Xie

引用次数: 0

Design and synthesis of polymer nanoparticles with pH-responsive pan-HDAC inhibitor (C5) derived from norbornene block copolymers to increase C5 solubility and improve its targeted delivery to prostate cancer sites. 基于降冰片烯嵌段共聚物的ph响应泛hdac抑制剂（C5）纳米聚合物的设计与合成，以提高C5的溶解度并改善其在前列腺癌部位的靶向递送。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-07-23 DOI: 10.1080/14756366.2025.2530557

Jacob Mathew, Anshul Mishra, Trong-Nghia Le, Jing-Ping Liou, Mei-Jung Lai, Vijayakameswara Rao Neralla

{"title":"Design and synthesis of polymer nanoparticles with pH-responsive pan-HDAC inhibitor (C5) derived from norbornene block copolymers to increase C5 solubility and improve its targeted delivery to prostate cancer sites.","authors":"Jacob Mathew, Anshul Mishra, Trong-Nghia Le, Jing-Ping Liou, Mei-Jung Lai, Vijayakameswara Rao Neralla","doi":"10.1080/14756366.2025.2530557","DOIUrl":"10.1080/14756366.2025.2530557","url":null,"abstract":"This study investigated the incorporation of C5, a pan-HDAC inhibitor, into a norbornene-derived block copolymer with pH-sensitive hydrolysis (PNEG-b-P(Nor-PABA-C5)) to generate NPs for prostate cancer treatment. Amphiphilic PNEG-b-P(Nor-PABA-C5) formed NPs in aqueous environments, with hydrophobic Nor-PABA-C5 monomers in the core and hydrophilic PNEG monomers on the surface. DLS analysis showed a particle size of 122 ± 12 nm with a PDI of 0.35, confirmed by SEM and TEM. TEM imaging revealed spherical morphology, enabling the NPs to transport hydrophobic pan-HDACi drugs to PC-3 tumour sites and facilitate release through hydrolysis under acidic conditions. The NPs exhibited pH-hydrolysis characteristics, with enhanced drug release (61 ± 1.7%) at pH 6.2 compared to pH 7.4 (35 ± 0.8%). MTT assay confirmed antiproliferative effect. Analysis of FITC/(PNEG-b-P(Nor-PABA-C5)) cellular uptake showed increased absorption in prostate tumours. Live/dead cell assays showed loss of viability, with increased red fluorescence and morphological disruption at higher concentrations over 48 and 72 h.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2530557"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12288175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690483","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

N-alkyl and N-benzyl indoles are anti-SARS-CoV-2 agents and nsp13 inhibitors. n -烷基和n -苄基吲哚是抗sars - cov -2药物和nsp13抑制剂。

IF 5.4 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-08-07 Epub Date: 2025-08-12 DOI: 10.1080/14756366.2025.2539445

Aurora Albano, Roberta Emmolo, Riccardo De Santis, Elisa Patacchini, Valentina Noemi Madia, Stefania Maloccu, Davide Ialongo, Giuseppe Ruggieri, Merve Arpacioglu, Luigi Scipione, Francesco Saccoliti, Donatella Amatore, Giorgia Grilli, Florigio Lista, Francesca Esposito, Enzo Tramontano, Angela Corona, Roberto Di Santo, Roberta Costi

{"title":"N-alkyl and N-benzyl indoles are anti-SARS-CoV-2 agents and nsp13 inhibitors.","authors":"Aurora Albano, Roberta Emmolo, Riccardo De Santis, Elisa Patacchini, Valentina Noemi Madia, Stefania Maloccu, Davide Ialongo, Giuseppe Ruggieri, Merve Arpacioglu, Luigi Scipione, Francesco Saccoliti, Donatella Amatore, Giorgia Grilli, Florigio Lista, Francesca Esposito, Enzo Tramontano, Angela Corona, Roberto Di Santo, Roberta Costi","doi":"10.1080/14756366.2025.2539445","DOIUrl":"10.1080/14756366.2025.2539445","url":null,"abstract":"COVID-19 pandemic stimulated tremendous efforts to develop therapeutic strategies targeting SARS-CoV-2, leading to the evaluation of a wide range of potential treatments in clinical trials. However, effective therapeutics remain elusive when the development of new variants and the limits of antiviral drugs is considered. Therefore, the development of antiviral drugs against SARS-CoV-2 is of paramount importance. Among potential drug targets, the SARS-CoV-2 nsp13 is highly attractive thanks to its pivotal role in viral replication. Pursuing our studies on the development of nsp13 inhibitors, in this work we describe the design, synthesis, and biological evaluation of novel inhibitors targeting SARS-CoV-2 nsp13. The newly designed N-benzyl indole derivatives were active against both enzymatic activities showing measurable IC50 under 30 μM concentration, while N-alkyl derivatives showed less promising results. Interestingly, the tested compounds blocked viral replication with no cytotoxicity. Docking studies predicted their binding into an allosteric conserved site located in the RecA2 domain.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2539445"},"PeriodicalIF":5.4,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144821514","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

In-cell bioluminescence resonance energy transfer (BRET)-based assay uncovers ceritinib and CA-074 as SARS-CoV-2 papain-like protease inhibitors. 基于细胞内生物发光共振能量转移（BRET）的检测发现 Ceritinib 和 CA-074 是 SARS-CoV-2 类木瓜蛋白酶抑制剂。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-08-20 DOI: 10.1080/14756366.2024.2387417

Mei Li, Zhu-Chun Bei, Yongtian Yuan, Baogang Wang, Dongna Zhang, Likun Xu, Liangliang Zhao, Qin Xu, Yabin Song

{"title":"In-cell bioluminescence resonance energy transfer (BRET)-based assay uncovers ceritinib and CA-074 as SARS-CoV-2 papain-like protease inhibitors.","authors":"Mei Li, Zhu-Chun Bei, Yongtian Yuan, Baogang Wang, Dongna Zhang, Likun Xu, Liangliang Zhao, Qin Xu, Yabin Song","doi":"10.1080/14756366.2024.2387417","DOIUrl":"10.1080/14756366.2024.2387417","url":null,"abstract":"Papain-like protease (PLpro) is an attractive anti-coronavirus target. The development of PLpro inhibitors, however, is hampered by the limitations of the existing PLpro assay and the scarcity of validated active compounds. We developed a novel in-cell PLpro assay based on BRET and used it to evaluate and discover SARS-CoV-2 PLpro inhibitors. The developed assay demonstrated remarkable sensitivity for detecting the reduction of intracellular PLpro activity while presenting high reliability and performance for inhibitor evaluation and high-throughput screening. Using this assay, three protease inhibitors were identified as novel PLpro inhibitors that are structurally disparate from those previously known. Subsequent enzymatic assays and ligand-protein interaction analysis based on molecular docking revealed that ceritinib directly inhibited PLpro, showing high geometric complementarity with the substrate-binding pocket in PLpro, whereas CA-074 methyl ester underwent intracellular hydrolysis, exposing a free carboxyhydroxyl group essential for hydrogen bonding with G266 in the BL2 groove, resulting in PLpro inhibition.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2387417"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11338211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008884","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

Synthesis and biological evaluation of quinoxaline derivatives as ASK1 inhibitors. 作为 ASK1 抑制剂的喹喔啉衍生物的合成和生物学评价。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-10-21 DOI: 10.1080/14756366.2024.2414382

Xiaorui Han, Pingping Lan, Qianfeng Chen, Hua Liu, Zhongwen Chen, Tiantian Wang, Zengtao Wang

引用次数: 0

Vitamin B6 inhibits activity of Helicobacter pylori adenylosuccinate synthetase and growth of reference and clinical, antibiotic-resistant H. pylori strains. 维生素 B6 可抑制幽门螺旋杆菌腺苷琥珀酸合成酶的活性以及参考菌株和临床抗生素耐药幽门螺旋杆菌菌株的生长。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-08-16 DOI: 10.1080/14756366.2024.2372734

Marta Ilona Wojtyś, Weronika Maksymiuk, Marta Narczyk, Ante Bubić, Ivana Leščić Ašler, Paweł Krzyżek, Grażyna Gościniak, Elżbieta Katarzyna Jagusztyn-Krynicka, Agnieszka Bzowska

{"title":"Vitamin B6 inhibits activity of Helicobacter pylori adenylosuccinate synthetase and growth of reference and clinical, antibiotic-resistant H. pylori strains.","authors":"Marta Ilona Wojtyś, Weronika Maksymiuk, Marta Narczyk, Ante Bubić, Ivana Leščić Ašler, Paweł Krzyżek, Grażyna Gościniak, Elżbieta Katarzyna Jagusztyn-Krynicka, Agnieszka Bzowska","doi":"10.1080/14756366.2024.2372734","DOIUrl":"10.1080/14756366.2024.2372734","url":null,"abstract":"The current therapies against gastric pathogen Helicobacter pylori are ineffective in over 20% of patients. Enzymes belonging to the purine salvage pathway are considered as novel drug targets in this pathogen. Therefore, the main aim of the current study was to determine the antibacterial activity of pyridoxal 5'-phosphate (PLP), an active form of vitamin B6, against reference and clinical strains of H. pylori. Using a broad set of microbiological, physicochemical (UV absorption, LC-MS, X-ray analysis) and in silico experiments, we were able to prove that PLP inhibits adenylosuccinate synthetase (AdSS) from H. pylori by the competition with GTP (IC50eq ∼30 nM). This behaviour was attributed to formation of a Schiff base with a lysine residue (a covalent bond with Lys322 in the GTP binding site of AdSS) and was potentiated by the presence of vitamin C. This antibacterial activity of PLP gives hope for its future use against H. pylori.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2372734"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988056","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