Journal of Enzyme Inhibition and Medicinal Chemistry最新文献_第6页

Expanding the antiprotozoal activity and the mechanism of action of n-butyl and iso-butyl ester of quinoxaline-1,4-di-N-oxide derivatives against Giardia lamblia, Trichomonas vaginalis, and Entamoeba histolytica. An in vitro and in silico approach. 拓展喹喔啉-1,4-二-N-氧化物正丁酯和异丁酯衍生物对蓝氏贾第鞭毛虫、阴道毛滴虫和组织溶解恩塔莫阿巴的抗原虫活性和作用机制。体外和硅学方法。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-10-29 DOI: 10.1080/14756366.2024.2413018

Alonzo González-González, Oscar Sánchez-Sánchez, Lilián Yépez-Mulia, Timoteo Delgado-Maldonado, Lenci K Vázquez-Jiménez, Gabriel López-Velázquez, José Ignacio de la Mora-de la Mora, Sebastian Pacheco-Gutierrez, Laura Chino-Ríos, Diego Arias, Adriana Moreno-Rodríguez, Alma Paz-González, Eyra Ortíz-Pérez, Gildardo Rivera

{"title":"Expanding the antiprotozoal activity and the mechanism of action of n-butyl and iso-butyl ester of quinoxaline-1,4-di-N-oxide derivatives against Giardia lamblia, Trichomonas vaginalis, and Entamoeba histolytica. An in vitro and in silico approach.","authors":"Alonzo González-González, Oscar Sánchez-Sánchez, Lilián Yépez-Mulia, Timoteo Delgado-Maldonado, Lenci K Vázquez-Jiménez, Gabriel López-Velázquez, José Ignacio de la Mora-de la Mora, Sebastian Pacheco-Gutierrez, Laura Chino-Ríos, Diego Arias, Adriana Moreno-Rodríguez, Alma Paz-González, Eyra Ortíz-Pérez, Gildardo Rivera","doi":"10.1080/14756366.2024.2413018","DOIUrl":"10.1080/14756366.2024.2413018","url":null,"abstract":"In this study, n-butyl and iso-butyl quinoxaline-7-carboxylate-1,4-di-N-oxide derivatives were evaluated in vitro against Giardia lamblia (G. lamblia), Trichomonas vaginalis (T. vaginalis), and Entamoeba histolytica (E. histolytica). The potential mechanism of action determination was approached by in silico analysis on G. lamblia and T. vaginalis triosephosphate isomerase (GlTIM and TvTIM, respectively), and on E. histolytica thioredoxin reductase (EhTrxR). Enzyme inactivation assays were performed on recombinant GlTIM and EhTrxR. Compound T-167 showed the best giardicidal activity (IC50 = 25.53 nM) and the highest inactivation efficiency against GlTIM without significantly perturbing its human homolog. Compounds T-142 and T-143 showed the best amoebicidal (IC50 = 9.20 nM) and trichomonacidal (IC50 = 45.20 nM) activity, respectively. Additionally, T-143 had a high activity as giardicial (IC50 = 29.13 nM) and amoebicidal (IC50 = 15.14 nM), proposing it as a broad-spectrum antiparasitic agent. Compounds T-145, and T-161 were the best EhTrxR inhibitors with IC50 of 16 µM, and 18 µM, respectively.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2413018"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521985","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

Anti-cancer activity and cellular uptake of 7,3',4'- and 7,8,4'-trihydroxyisoflavone in HepG2 cells under hypoxic conditions. 缺氧条件下 7,3',4'- 和 7,8,4'- 三羟基异黄酮在 HepG2 细胞中的抗癌活性和细胞吸收。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2023-12-28 DOI: 10.1080/14756366.2023.2288806

Wen-Sheng Tzeng, Wei-Lin Teng, Pao-Hsien Huang, Feng-Lin Yen, Yow-Ling Shiue

{"title":"Anti-cancer activity and cellular uptake of 7,3',4'- and 7,8,4'-trihydroxyisoflavone in HepG2 cells under hypoxic conditions.","authors":"Wen-Sheng Tzeng, Wei-Lin Teng, Pao-Hsien Huang, Feng-Lin Yen, Yow-Ling Shiue","doi":"10.1080/14756366.2023.2288806","DOIUrl":"10.1080/14756366.2023.2288806","url":null,"abstract":"Transarterial chemoembolisation (TACE) is used for unresectable hepatocellular carcinoma (HCC) treatment, but TACE-induced hypoxia leads to poor prognosis. The anti-cancer effects of soybean isoflavones daidzein derivatives 7,3',4'-trihydroxyisoflavone (734THIF) and 7,8,4'-trihydroxyisoflavone (784THIF) were evaluated under hypoxic microenvironments. Molecular docking of these isomers with cyclooxygenase-2 (COX-2) and vascular endothelial growth factor receptor 2 (VEGFR2) was assessed. About 40 μM of 734THIF and 784THIF have the best effect on inhibiting the proliferation of HepG2 cells under hypoxic conditions. At a concentration of 40 μM, 784THIF significantly inhibits COX-2 expression in pre-hypoxia conditions compared to 734THIF, with an inhibition rate of 67.73%. Additionally, 40 μM 784THIF downregulates the expression of hypoxic, inflammatory, and metastatic-related proteins, regulates oxidative stress, and inhibits the expression of anti-apoptotic proteins. The uptake by HepG2 confirmed higher 784THIF level and slower degradation characteristics under post- or pre-hypoxic conditions. In conclusion, our results showed that 784THIF had better anti-cancer effects and cellular uptake than 734THIF.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2288806"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10763887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048863","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

Development of novel ALOX15 inhibitors combining dual machine learning filtering and fragment substitution optimisation approaches, molecular docking and dynamic simulation methods. 结合双重机器学习过滤和片段置换优化方法、分子对接和动态模拟方法，开发新型 ALOX15 抑制剂。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-01-12 DOI: 10.1080/14756366.2024.2301756

Yinglin Liao, Peng Cao, Lianxiang Luo

引用次数: 0

Effects of thymoquinone and the curcumin analog EF-24 on the activity of the enzyme paraoxonase-1 in human glioblastoma cells U87MG. 胸腺醌和姜黄素类似物 EF-24 对人胶质母细胞瘤细胞 U87MG 中副氧合酶-1 活性的影响。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-06-12 DOI: 10.1080/14756366.2024.2339901

Ender Simsek, Asuman Sunguroglu, Ahmet Kilic, Nurbanu Özgültekin, O Ozensoy Guler

引用次数: 0

Cloning, expression, and purification of an α-carbonic anhydrase from Toxoplasma gondii to unveil its kinetic parameters and anion inhibition profile. 从弓形虫中克隆、表达和纯化一种α-碳酸酐酶，以揭示其动力学参数和阴离子抑制曲线。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-06-07 DOI: 10.1080/14756366.2024.2346523

Viviana De Luca, Simone Giovannuzzi, Clemente Capasso, Claudiu T Supuran

{"title":"Cloning, expression, and purification of an α-carbonic anhydrase from Toxoplasma gondii to unveil its kinetic parameters and anion inhibition profile.","authors":"Viviana De Luca, Simone Giovannuzzi, Clemente Capasso, Claudiu T Supuran","doi":"10.1080/14756366.2024.2346523","DOIUrl":"10.1080/14756366.2024.2346523","url":null,"abstract":"Toxoplasmosis, induced by the intracellular parasite Toxoplasma gondii, holds considerable implications for global health. While treatment options primarily focusing on folate pathway enzymes have notable limitations, current research endeavours concentrate on pinpointing specific metabolic pathways vital for parasite survival. Carbonic anhydrases (CAs, EC 4.2.1.1) have emerged as potential drug targets due to their role in fundamental reactions critical for various protozoan metabolic processes. Within T. gondii, the Carbonic Anhydrase-Related Protein (TgCA_RP) plays a pivotal role in rhoptry biogenesis. Notably, α-CA (TcCA) from another protozoan, Trypanosoma cruzi, exhibited considerable susceptibility to classical CA inhibitors (CAIs) such as anions, sulphonamides, thiols, and hydroxamates. Here, the recombinant DNA technology was employed to synthesise and clone the identified gene in the T. gondii genome, which encodes an α-CA protein (Tg_CA), with the purpose of heterologously overexpressing its corresponding protein. Tg_CA kinetic constants were determined, and its inhibition patterns explored with inorganic metal-complexing compounds, which are relevant for rational compound design. The significance of this study lies in the potential development of innovative therapeutic strategies that disrupt the vital metabolic pathways crucial for T. gondii survival and virulence. This research may lead to the development of targeted treatments, offering new approaches to manage toxoplasmosis.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2346523"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11163988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283871","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

Novel dual-targeting inhibitors of NSD2 and HDAC2 for the treatment of liver cancer: structure-based virtual screening, molecular dynamics simulation, and in vitro and in vivo biological activity evaluations. 新型NSD2和HDAC2双靶向抑制剂治疗肝癌:基于结构的虚拟筛选、分子动力学模拟和体内外生物活性评价

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2023-12-07 DOI: 10.1080/14756366.2023.2289355

Xing Jin, Yuting Wang, Jing Chen, Miaomiao Niu, Yang Yang, Qiaoxuan Zhang, Guangyu Bao

{"title":"Novel dual-targeting inhibitors of NSD2 and HDAC2 for the treatment of liver cancer: structure-based virtual screening, molecular dynamics simulation, and in vitro and in vivo biological activity evaluations.","authors":"Xing Jin, Yuting Wang, Jing Chen, Miaomiao Niu, Yang Yang, Qiaoxuan Zhang, Guangyu Bao","doi":"10.1080/14756366.2023.2289355","DOIUrl":"10.1080/14756366.2023.2289355","url":null,"abstract":"Liver cancer exhibits a high degree of heterogeneity and involves intricate mechanisms. Recent research has revealed the significant role of histone lysine methylation and acetylation in the epigenetic regulation of liver cancer development. In this study, five inhibitors capable of targeting both histone lysine methyltransferase nuclear receptor-binding SET domain 2 (NSD2) and histone deacetylase 2 (HDAC2) were identified using a structure-based virtual screening approach. Notably, DT-NH-1 displayed a potent inhibition of NSD2 (IC50 = 0.08 ± 0.03 μM) and HDAC2 (IC50 = 5.24 ± 0.87 nM). DT-NH-1 also demonstrated a strong anti-proliferative activity against various liver cancer cell lines, particularly HepG2 cells, and exhibited a high level of biological safety. In an experimental xenograft model involving HepG2 cells, DT-NH-1 showed a significant reduction in tumour growth. Consequently, these findings indicate that DT-NH-1 will be a promising lead compound for the treatment of liver cancer with epigenetic dual-target inhibitors.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2289355"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11721945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138498512","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

3-aryl-4-(3,4,5-trimethoxyphenyl)pyridines inhibit tubulin polymerisation and act as anticancer agents. 3-芳基-4-(3,4,5-三甲氧基苯基)吡啶抑制微管蛋白聚合，可作为抗癌剂。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2023-12-11 DOI: 10.1080/14756366.2023.2286939

Chao Wang, Yujing Zhang, Shanbo Yang, Lingyu Shi, Yutao Xiu, Yudong Wu, Hongfei Jiang

引用次数: 0

Druggable cavities and allosteric modulators of the cell division cycle 7 (CDC7) kinase. 细胞分裂周期 7 (CDC7) 激酶的药腔和异位调节剂。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-01-11 DOI: 10.1080/14756366.2024.2301767

Elisa Rojas-Prats, Loreto Martinez-Gonzalez, Carmen Gil, David Ramírez, Ana Martinez

引用次数: 0

Palindromic carbazole derivatives: unveiling their antiproliferative effect via topoisomerase II catalytic inhibition and apoptosis induction. 多环咔唑衍生物：通过拓扑异构酶 II 催化抑制和诱导细胞凋亡揭示其抗增殖作用

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-01-14 DOI: 10.1080/14756366.2024.2302920

Mateusz Olszewski, Natalia Maciejewska, Anoop Kallingal, Agnieszka Chylewska, Aleksandra M Dąbrowska, Małgorzata Biedulska, Mariusz Makowski, José M Padrón, Maciej Baginski

{"title":"Palindromic carbazole derivatives: unveiling their antiproliferative effect via topoisomerase II catalytic inhibition and apoptosis induction.","authors":"Mateusz Olszewski, Natalia Maciejewska, Anoop Kallingal, Agnieszka Chylewska, Aleksandra M Dąbrowska, Małgorzata Biedulska, Mariusz Makowski, José M Padrón, Maciej Baginski","doi":"10.1080/14756366.2024.2302920","DOIUrl":"10.1080/14756366.2024.2302920","url":null,"abstract":"Human DNA topoisomerases are essential for crucial cellular processes, including DNA replication, transcription, chromatin condensation, and maintenance of its structure. One of the significant strategies employed in cancer treatment involves the inhibition of a specific type of topoisomerase, known as topoisomerase II (Topo II). Carbazole derivatives, recognised for their varied biological activities, have recently become a significant focus in oncological research. This study assesses the efficacy of three symmetrically substituted carbazole derivatives: 2,7-Di(2-furyl)-9H-carbazole (27a), 3,6-Di(2-furyl)-9H-carbazole (36a), and 3,6-Di(2-thienyl)-9H-carbazole (36b) - as anticancer agents. Among investigated carbazole derivatives, compound 3,6-di(2-furyl)-9H-carbazole bearing two furan moieties emerged as a novel catalytic inhibitor of Topo II. Notably, 3,6-di(2-furyl)-9H-carbazole effectively selectively inhibited the relaxation and decatenation activities of Topo IIα, with minimal effects on the IIβ isoform. These findings underscore the potential of compound 3,6-Di(2-furyl)-9H-carbazole as a promising lead candidate warranting further investigation in the realm of anticancer drug development.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2302920"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10791108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139466698","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

Fluorinated indeno-quinoxaline bearing thiazole moieties as hypoglycaemic agents targeting α-amylase, and α-glucosidase: synthesis, molecular docking, and ADMET studies. 以α-淀粉酶和α-葡萄糖苷酶为靶标的含噻唑分子的氟化茚喹喔啉类降血糖药：合成、分子对接和 ADMET 研究。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-06-24 DOI: 10.1080/14756366.2024.2367128

Nirvana A Gohar, Eman A Fayed, Yousry A Ammar, Ola A Abu Ali, Ahmed Ragab, Amal M Mahfoz, Moustafa S Abusaif

{"title":"Fluorinated indeno-quinoxaline bearing thiazole moieties as hypoglycaemic agents targeting α-amylase, and α-glucosidase: synthesis, molecular docking, and ADMET studies.","authors":"Nirvana A Gohar, Eman A Fayed, Yousry A Ammar, Ola A Abu Ali, Ahmed Ragab, Amal M Mahfoz, Moustafa S Abusaif","doi":"10.1080/14756366.2024.2367128","DOIUrl":"10.1080/14756366.2024.2367128","url":null,"abstract":"Inhibition of α-glucosidase and α-amylase are key tactics for managing blood glucose levels. Currently, stronger, and more accessible inhibitors are needed to treat diabetes. Indeno[1,2-b] quinoxalines-carrying thiazole hybrids 1-17 were created and described using NMR. All analogues were tested for hypoglycaemic effect against STZ-induced diabetes in mice. Compounds 4, 6, 8, and 16 were the most potent among the synthesised analogues. These hybrids were examined for their effects on plasma insulin, urea, creatinine, GSH, MDA, ALT, AST, and total cholesterol. Moreover, these compounds were tested against α-glucosidase and α-amylase enzymes in vitro. The four hybrids 4, 6, 8, and 16 represented moderate to potent activity with IC50 values 0.982 ± 0.04, to 10.19 ± 0.21 for α-glucosidase inhibition and 17.58 ± 0.74 to 121.6 ± 5.14 μM for α-amylase inhibition when compared to the standard medication acarbose with IC50=0.316 ± 0.02 μM for α-glucosidase inhibition and 31.56 ± 1.33 μM for α-amylase inhibition. Docking studies as well as in silico ADMT were done.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2367128"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC467095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446338","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