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

Discovery of novel anaplastic lymphoma kinase (ALK) and histone deacetylase (HDAC) dual inhibitors exhibiting antiproliferative activity against non-small cell lung cancer. 发现新型无性淋巴瘤激酶（ALK）和组蛋白去乙酰化酶（HDAC）双重抑制剂，对非小细胞肺癌具有抗增殖活性。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-03-11 DOI: 10.1080/14756366.2024.2318645

Kang-Li Wang, Tsung-Yu Yeh, Pei-Chen Hsu, Tzu-Hsuan Wong, Jia-Rong Liu, Ji-Wang Chern, Miao-Hsia Lin, Chao-Wu Yu

{"title":"Discovery of novel anaplastic lymphoma kinase (ALK) and histone deacetylase (HDAC) dual inhibitors exhibiting antiproliferative activity against non-small cell lung cancer.","authors":"Kang-Li Wang, Tsung-Yu Yeh, Pei-Chen Hsu, Tzu-Hsuan Wong, Jia-Rong Liu, Ji-Wang Chern, Miao-Hsia Lin, Chao-Wu Yu","doi":"10.1080/14756366.2024.2318645","DOIUrl":"10.1080/14756366.2024.2318645","url":null,"abstract":"A series of novel benzimidazole derivatives were designed and synthesised based on the structures of reported oral available ALK inhibitor and HDAC inhibitor, pracinostat. In enzymatic assays, compound 3b, containing a 2-acyliminobenzimidazole moiety and hydroxamic acid side chain, could inhibit both ALK and HDAC6 (IC50 = 16 nM and 1.03 µM, respectively). Compound 3b also inhibited various ALK mutants known to be involved in crizotinib resistance, including mutant L1196M (IC50, 4.9 nM). Moreover, 3b inhibited the proliferation of several cancer cell lines, including ALK-addicted H2228 cells. To evaluate its potential for treating cancers in vivo, 3b was used in a human A549 xenograft model with BALB/c nude mice. At 20 mg/kg, 3b inhibited tumour growth by 85% yet had a negligible effect on mean body weight. These results suggest a attracting route for the further research and optimisation of dual ALK/HDAC inhibitors.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2318645"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10930102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140094175","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 evaluation of novel stilbene derivatives that degrade acidic nucleoplasmic DNA-binding protein 1 (And1) and synergize with PARP1 inhibitor in NSCLC cells. 设计、合成和评估能降解酸性核质 DNA 结合蛋白 1 (And1) 并与 PARP1 抑制剂协同作用于 NSCLC 细胞的新型二苯乙烯衍生物。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-07-29 DOI: 10.1080/14756366.2024.2383886

Leyuan Chen, Zhonghao Ren, Yunze Zhang, Wenbin Hou, Yiliang Li

{"title":"Design, synthesis, and evaluation of novel stilbene derivatives that degrade acidic nucleoplasmic DNA-binding protein 1 (And1) and synergize with PARP1 inhibitor in NSCLC cells.","authors":"Leyuan Chen, Zhonghao Ren, Yunze Zhang, Wenbin Hou, Yiliang Li","doi":"10.1080/14756366.2024.2383886","DOIUrl":"10.1080/14756366.2024.2383886","url":null,"abstract":"Specifically inducing the degradation of acidic nucleoplasmic DNA-binding protein 1 (And1) is a promising antitumor strategy. Our previous study identified Bazedoxifene (BZA) and CH3 as specific And1 degraders and validated their activity in reversing radiotherapy resistance in vitro and in vivo. However, unelucidated structure-activity relationships and moderate activity have limited their application. In this study, 27 novel CH3 derivatives were designed and synthesised based on the cavity topology of the WD40 domain of And1. Among them, A15 with a \"V\" conformation significantly induced And1 degradation in NSCLC cells. In addition, this study demonstrated a potential synthetic lethal effect of And1 degraders and PARP1 inhibitors. 1 µM of Olaparib in combination with 5 µM of A15 significantly inhibited the proliferation of A549 and H460 cells. Overall, these compounds are valuable tools for elucidating And1 biology, and their special spatial conformation make them promising candidates for future optimisation studies.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2383886"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11288208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788224","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, in vitro and in vivo biological evaluation of pterostilbene derivatives for anti-inflammation therapy. 用于抗炎治疗的紫檀芪衍生物的设计、合成、体外和体内生物学评价。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-02-29 DOI: 10.1080/14756366.2024.2315227

Liuzeng Chen, Ke Wang, Xiaohan Liu, Lifan Wang, Hui Zou, Shuying Hu, Lingling Zhou, Rong Li, Shiying Cao, Banfeng Ruan, Quanren Cui

{"title":"Design, synthesis, in vitro and in vivo biological evaluation of pterostilbene derivatives for anti-inflammation therapy.","authors":"Liuzeng Chen, Ke Wang, Xiaohan Liu, Lifan Wang, Hui Zou, Shuying Hu, Lingling Zhou, Rong Li, Shiying Cao, Banfeng Ruan, Quanren Cui","doi":"10.1080/14756366.2024.2315227","DOIUrl":"10.1080/14756366.2024.2315227","url":null,"abstract":"Pterostilbene (PST) is a naturally derived stilbene compound in grapes, blueberries, and other fruits. It is also a natural dietary compound with a wide range of biological activities such as antioxidant, anti-inflammatory, antitumor, and so on. Structural modifications based on the chemical scaffold of the pterostilbene skeleton are of great importance for drug discovery. In this study, pterostilbene skeletons were used to design novel anti-inflammatory compounds with high activity and low toxicity. A total of 30 new were found and synthesised, and their anti-inflammatory activity and safety were screened. Among them, compound E2 was the most active (against NO: IC50 = 0.7 μM) than celecoxib. Further studies showed that compound E2 exerted anti-inflammatory activity by blocking LPS-induced NF-κB/MAPK signalling pathway activation. In vivo experiments revealed that compound E2 had a good alleviating effect on acute colitis in mice. In conclusion, compound E2 may be a promising anti-inflammatory lead compound.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2315227"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10906133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139990276","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

Click estradiol dimers with novel aromatic bridging units: synthesis and anticancer evaluation. 具有新型芳香族桥接单元的点击雌二醇二聚体：合成与抗癌评估。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-06-21 DOI: 10.1080/14756366.2024.2367139

Jiří Řehulka, Michal Jurášek, Pavel Dráber, Aleksandra Ivanová, Soňa Gurská, Kateřina Ječmeňová, Olena Mokshyna, Marián Hajdúch, Pavel Polishchuk, Pavel B Drašar, Petr Džubák

{"title":"Click estradiol dimers with novel aromatic bridging units: synthesis and anticancer evaluation.","authors":"Jiří Řehulka, Michal Jurášek, Pavel Dráber, Aleksandra Ivanová, Soňa Gurská, Kateřina Ječmeňová, Olena Mokshyna, Marián Hajdúch, Pavel Polishchuk, Pavel B Drašar, Petr Džubák","doi":"10.1080/14756366.2024.2367139","DOIUrl":"10.1080/14756366.2024.2367139","url":null,"abstract":"Estradiol dimers (EDs) possess significant anticancer activity by targeting tubulin dynamics. In this study, we synthesised 12 EDs variants via copper-catalysed azide-alkyne cycloaddition (CuAAC) reaction, focusing on structural modifications within the aromatic bridge connecting two estradiol moieties. In vitro testing of these EDs revealed a marked improvement in selectivity towards cancerous cells, particularly for ED1-8. The most active compounds, ED3 (IC50 = 0.38 μM in CCRF-CEM) and ED5 (IC50 = 0.71 μM in CCRF-CEM) demonstrated cytotoxic effects superior to 2-methoxyestradiol (IC50 = 1.61 μM in CCRF-CEM) and exhibited anti-angiogenic properties in an endothelial cell tube-formation model. Cell-based experiments and in vitro assays revealed that EDs interfere with mitotic spindle assembly. Additionally, we proposed an in silico model illustrating the probable binding modes of ED3 and ED5, suggesting that dimers with a simple linker and a single substituent on the aromatic central ring possess enhanced characteristics compared to more complex dimers.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2367139"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC467089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432071","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

Non-small cell lung cancer sensitisation to platinum chemotherapy via new thiazole-triazole hybrids acting as dual T-type CCB/MMP-9 inhibitors. 通过新型噻唑-三唑混合物作为 T 型 CCB/MMP-9 双重抑制剂提高非小细胞肺癌对铂化疗的敏感性。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-08-14 DOI: 10.1080/14756366.2024.2388209

Hassan Gamal, Khadiga A Ismail, A-Mohsen M E Omar, Mohamed Teleb, Marwa M Abu-Serie, Sun Huang, Abdalla S Abdelsattar, Gerald W Zamponi, Hesham Fahmy

{"title":"Non-small cell lung cancer sensitisation to platinum chemotherapy via new thiazole-triazole hybrids acting as dual T-type CCB/MMP-9 inhibitors.","authors":"Hassan Gamal, Khadiga A Ismail, A-Mohsen M E Omar, Mohamed Teleb, Marwa M Abu-Serie, Sun Huang, Abdalla S Abdelsattar, Gerald W Zamponi, Hesham Fahmy","doi":"10.1080/14756366.2024.2388209","DOIUrl":"10.1080/14756366.2024.2388209","url":null,"abstract":"Cisplatin remains the unchallenged standard therapy for NSCLC. However, it is not completely curative due to drug resistance and oxidative stress-induced toxicity. Drug resistance is linked to overexpression of matrix metalloproteinases (MMPs) and aberrant calcium signalling. We report synthesis of novel thiazole-triazole hybrids as MMP-9 inhibitors with T-type calcium channel blocking and antioxidant effects to sensitise NSCLC to cisplatin and ameliorate its toxicity. MTT and whole cell patch clamp assays revealed that 6d has a balanced profile of cytotoxicity (IC50 = 21 ± 1 nM, SI = 12.14) and T-type calcium channel blocking activity (⁓60% at 10 μM). It exhibited moderate ROS scavenging activity and nanomolar MMP-9 inhibition (IC50 = 90 ± 7 nM) surpassing NNGH with MMP-9 over -2 and MMP-10 over -13 selectivity. Docking and MDs simulated its receptor binding mode. Combination studies confirmed that 6d synergized with cisplatin (CI = 0.69 ± 0.05) lowering its IC50 by 6.89 folds. Overall, the study introduces potential lead adjuvants for NSCLC platinum-based therapy.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2388209"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11328607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975776","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 evaluation of marine naphthoquinone-naphthol derivatives as potential anticancer agents. 作为潜在抗癌剂的海洋萘醌-萘酚衍生物的设计、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: 2024-10-15 DOI: 10.1080/14756366.2024.2412865

Yujuan Li, Luyou Yelv, Xiaoqiu Wu, Ning Liu, Yamin Zhu

{"title":"Design, synthesis and biological evaluation of marine naphthoquinone-naphthol derivatives as potential anticancer agents.","authors":"Yujuan Li, Luyou Yelv, Xiaoqiu Wu, Ning Liu, Yamin Zhu","doi":"10.1080/14756366.2024.2412865","DOIUrl":"https://doi.org/10.1080/14756366.2024.2412865","url":null,"abstract":"1'-Hydroxy-4',8,8'-trimethoxy-[2,2'-binaphthalene]-1,4-dione (compound 5), a secondary metabolite recently discovered in marine fungi, demonstrates promising cytotoxic and anticancer potential. However, knowledge regarding the anticancer activities and biological mechanisms of its derivatives remains limited. Herein, a series of novel naphthoquinone-naphthol derivatives were designed, synthesised, and evaluated for their anticancer activity against cancer cells of different origins. Among these, Compound 13, featuring an oxopropyl group at the ortho-position of quinone group, exhibited the most potent inhibitory effects on HCT116, PC9, and A549 cells, with IC50 values decreasing from 5.27 to 1.18 μM (4.5-fold increase), 6.98 to 0.57 μM (12-fold increase), and 5.88 to 2.25 μM (2.6-fold increase), respectively, compared to compound 5. Further mechanistic studies revealed that compound 13 significantly induced cell apoptosis by increasing the expression levels of cleaved caspase-3 and reducing Bcl-2 proteins through downregulating the EGFR/PI3K/Akt signalling pathway, leading to the inhibition of proliferation in HCT116 and PC9 cells. The present findings suggest this novel naphthoquinone-naphthol derivative may hold potential as an anticancer therapeutic lead.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2412865"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11486183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467263","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 optimization and molecular dynamics studies of new tumor-selective s-triazines targeting DNA and MMP-10/13 for halting colorectal and secondary liver cancers. 针对 DNA 和 MMP-10/13 的新型肿瘤选择性 s-三嗪的结构优化和分子动力学研究，用于阻止结直肠癌和继发性肝癌的发生。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-11-08 DOI: 10.1080/14756366.2024.2423174

Christine A Morcos, Nesreen S Haiba, Rafik W Bassily, Marwa M Abu-Serie, Amira F El-Yazbi, Omar A Soliman, Sherine N Khattab, Mohamed Teleb

{"title":"Structure optimization and molecular dynamics studies of new tumor-selective s-triazines targeting DNA and MMP-10/13 for halting colorectal and secondary liver cancers.","authors":"Christine A Morcos, Nesreen S Haiba, Rafik W Bassily, Marwa M Abu-Serie, Amira F El-Yazbi, Omar A Soliman, Sherine N Khattab, Mohamed Teleb","doi":"10.1080/14756366.2024.2423174","DOIUrl":"10.1080/14756366.2024.2423174","url":null,"abstract":"A series of triazole-tethered triazines bearing pharmacophoric features of DNA-targeting agents and non-hydroxamate MMPs inhibitors were synthesized and screened against HCT-116, Caco-2 cells, and normal colonocytes by MTT assay. 7a and 7g surpassed doxorubicin against HCT-116 cells regarding potency (IC50 = 0.87 and 1.41 nM) and safety (SI = 181.93 and 54.41). 7g was potent against liver cancer (HepG-2; IC50 = 65.08 nM), the main metastatic site of CRC with correlation to MMP-13 expression. Both derivatives induced DNA damage at 2.67 and 1.87 nM, disrupted HCT-116 cell cycle and triggered apoptosis by 33.17% compared to doxorubicin (DNA damage at 0.76 nM and 40.21% apoptosis induction). 7g surpassed NNGH against MMP-10 (IC50 = 0.205 μM) and MMP-13 (IC50 = 0.275 μM) and downregulated HCT-116 VEGF related to CRC progression by 38%. Docking and MDs simulated ligands-receptors binding modes and highlighted SAR. Their ADMET profiles, drug-likeness and possible off-targets were computationally predicted.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2423174"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604651","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. 更正。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2023-12-21 DOI: 10.1080/14756366.2023.2297117

引用次数: 0

Targeting the glutamine-arginine-proline metabolism axis in cancer. 针对癌症中的谷氨酰胺-精氨酸-脯氨酸代谢轴。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-07-25 DOI: 10.1080/14756366.2024.2367129

Di Wang, Jiang-Jie Duan, Yu-Feng Guo, Jun-Jie Chen, Tian-Qing Chen, Jun Wang, Shi-Cang Yu

引用次数: 0

Dihydroartemisinin enhances the anti-tumour effect of photodynamic therapy by targeting PKM2-mediated glycolysis in oesophageal cancer cell. 双氢青蒿素通过靶向 PKM2 介导的食道癌细胞糖酵解增强光动力疗法的抗肿瘤效果

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2023-12-18 DOI: 10.1080/14756366.2023.2296695

Mengru Jin, Luyao Shi, Li Wang, Dingyuan Zhang, Yanjing Li

引用次数: 0