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

Design, synthesis, and apoptotic antiproliferative action of new 1,2,3-triazole/1,2,4-oxadiazole hybrids as dual EGFR/VEGFR-2 inhibitors. 新型 1,2,3-三唑/1,2,4-恶二唑混合物作为表皮生长因子受体/表皮生长因子受体-2 双重抑制剂的设计、合成和凋亡抗增殖作用。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-02-07 DOI: 10.1080/14756366.2024.2305856

Mohamed A Mahmoud, Anber F Mohammed, Ola I A Salem, Tahani Mazyad Almutairi, Stefan Bräse, Bahaa G M Youssif

{"title":"Design, synthesis, and apoptotic antiproliferative action of new 1,2,3-triazole/1,2,4-oxadiazole hybrids as dual EGFR/VEGFR-2 inhibitors.","authors":"Mohamed A Mahmoud, Anber F Mohammed, Ola I A Salem, Tahani Mazyad Almutairi, Stefan Bräse, Bahaa G M Youssif","doi":"10.1080/14756366.2024.2305856","DOIUrl":"10.1080/14756366.2024.2305856","url":null,"abstract":"A novel series of 1,2,3-triazole/1,2,4-oxadiazole hybrids (7a-o) was developed as dual inhibitors of EGFR/VEGFR-2. Compounds 7a-o were evaluated as antiproliferative agents with Erlotinib as the reference drug. Results demonstrated that most of the tested compounds showed significant antiproliferative action with GI50 values ranging from 28 to 104 nM, compared to Erlotinib (GI50 = 33 nM), and compounds 7i-m were the most potent. Compounds 7h, 7i, 7j, 7k, and 7l were evaluated as dual EGFR/VEGFR-2 inhibitors. These in vitro experiments demonstrated that compounds 7j, 7k, and 7l are potent antiproliferative agents that may operate as dual EGFR/VEGFR-2 inhibitors. Compounds 7j, 7k, and 7l were evaluated for their apoptotic potential activity, where findings indicated that compounds 7j, 7k, and 7l promote apoptosis by activating caspase-3, 8, and Bax and down-regulating the anti-apoptotic Bcl-2. Molecular docking simulations show the binding mode of the most active antiproliferative compounds within EGFR and VEGFR-2 active sites.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2305856"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10854447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139702683","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

Discovery of natural anthraquinones as potent inhibitors against pancreatic lipase: structure-activity relationships and inhibitory mechanism. 发现可作为胰脂肪酶强效抑制剂的天然蒽醌类化合物：结构-活性关系和抑制机制。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-09-02 DOI: 10.1080/14756366.2024.2398561

Zi-Qiang Chen, Wen-Yao He, Si-Yuan Yang, Hong-Hong Ma, Jing Zhou, Hao Li, Ya-Di Zhu, Xing-Kai Qian, Li-Wei Zou

{"title":"Discovery of natural anthraquinones as potent inhibitors against pancreatic lipase: structure-activity relationships and inhibitory mechanism.","authors":"Zi-Qiang Chen, Wen-Yao He, Si-Yuan Yang, Hong-Hong Ma, Jing Zhou, Hao Li, Ya-Di Zhu, Xing-Kai Qian, Li-Wei Zou","doi":"10.1080/14756366.2024.2398561","DOIUrl":"10.1080/14756366.2024.2398561","url":null,"abstract":"Obesity is acknowledged as a significant risk factor for various metabolic diseases, and the inhibition of human pancreatic lipase (hPL) can impede lipid digestion and absorption, thereby offering potential benefits for obesity treatment. Anthraquinones is a kind of natural and synthetic compounds with wide application. In this study, the inhibitory effects of 31 anthraquinones on hPL were evaluated. The data shows that AQ7, AQ26, and AQ27 demonstrated significant inhibitory activity against hPL, and exhibited selectivity towards other known serine hydrolases. Then the structure-activity relationship between anthraquinones and hPL was further analysed. AQ7 was found to be a mixed inhibition of hPL through inhibition kinetics, while AQ26 and AQ27 were effective non-competitive inhibition of hPL. Molecular docking data revealed that AQ7, AQ26, and AQ27 all could associate with the site of hPL. Developing hPL inhibitors for obesity prevention and treatment could be simplified with this novel and promising lead compound.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2398561"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119987","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

Exploring of N-phthalimide-linked 1,2,3-triazole analogues with promising -anti-SARS-CoV-2 activity: synthesis, biological screening, and molecular modelling studies. 探索具有良好抗 SARS-CoV-2 活性的 N-邻苯二甲酰亚胺连接的 1,2,3-三唑类似物：合成、生物筛选和分子建模研究。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-06-07 DOI: 10.1080/14756366.2024.2351861

Ateyatallah Aljuhani, Mosa Alsehli, Mohamed A Seleem, Shaya Y Alraqa, Hany E A Ahmed, Nadjet Rezki, Mohamed R Aouad

{"title":"Exploring of N-phthalimide-linked 1,2,3-triazole analogues with promising -anti-SARS-CoV-2 activity: synthesis, biological screening, and molecular modelling studies.","authors":"Ateyatallah Aljuhani, Mosa Alsehli, Mohamed A Seleem, Shaya Y Alraqa, Hany E A Ahmed, Nadjet Rezki, Mohamed R Aouad","doi":"10.1080/14756366.2024.2351861","DOIUrl":"10.1080/14756366.2024.2351861","url":null,"abstract":"In this study, a library of phthalimide Schiff base linked to 1,4-disubstituted-1,2,3-triazoles was designed, synthesised, and characterised by different spectral analyses. All analogues have been introduced for in vitro assay of their antiviral activity against COVID-19 virus using Vero cell as incubator with different concentrations. The data revealed most of these derivatives showed potent cellular anti-COVID-19 activity and prevent viral growth by more than 90% at two different concentrations with no or weak cytotoxic effect on Vero cells. Furthermore, in vitro assay was done against this enzyme for all analogues and the results showed two of them have IC50 data by 90 µM inhibitory activity. An extensive molecular docking simulation was run to analyse their antiviral mechanism that found the proper non-covalent interaction within the Mpro protease enzyme. Finally, we profiled two reversible inhibitors, COOH and F substituted analogues that might be promising drug candidates for further development have been discovered.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2351861"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11164105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283872","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

Crystal structure of dihydroneopterin aldolase from Mycobacterium tuberculosis associated with 8-mercaptoguanine, and development of novel S8-functionalized analogues as inhibitors: Synthesis, enzyme inhibition, in vitro toxicity and antitubercular activity. 与 8-巯基鸟嘌呤相关的结核分枝杆菌二氢蝶呤醛缩酶的晶体结构，以及作为抑制剂的新型 S8 功能化类似物的开发：合成、酶抑制、体外毒性和抗结核活性。

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: 10.1080/14756366.2024.2388207

Alexia de Matos Czeczot, Mauro Neves Muniz, Marcia Alberton Perelló, Éverton Edésio Dinis Silva, Luís Fernando Saraiva Macedo Timmers, Andresa Berger, Laura Calle Gonzalez, Guilherme Arraché Gonçalves, Sidnei Moura, Pablo Machado, Cristiano Valim Bizarro, Luiz Augusto Basso

{"title":"Crystal structure of dihydroneopterin aldolase from Mycobacterium tuberculosis associated with 8-mercaptoguanine, and development of novel S8-functionalized analogues as inhibitors: Synthesis, enzyme inhibition, in vitro toxicity and antitubercular activity.","authors":"Alexia de Matos Czeczot, Mauro Neves Muniz, Marcia Alberton Perelló, Éverton Edésio Dinis Silva, Luís Fernando Saraiva Macedo Timmers, Andresa Berger, Laura Calle Gonzalez, Guilherme Arraché Gonçalves, Sidnei Moura, Pablo Machado, Cristiano Valim Bizarro, Luiz Augusto Basso","doi":"10.1080/14756366.2024.2388207","DOIUrl":"10.1080/14756366.2024.2388207","url":null,"abstract":"The crystallographic structure of the FolB enzyme from Mycobacterium tuberculosis (MtFolB), complexed with its inhibitor 8-mercaptoguanine (8-MG), was elucidated at a resolution of 1.95 Å. A novel series of S8-functionalized 8-MG derivatives were synthesised and evaluated as in vitro inhibitors of dihydroneopterin aldolase (DHNA, EC 4.1.2.25) activity of MtFolB. These compounds exhibited IC50 values in the submicromolar range. Evaluation of the activity for five compounds indicated their inhibition mode and inhibition constants. Molecular docking analyses were performed to determine the enzyme-inhibitor intermolecular interactions and ligand conformations upon complex formation. The inhibitory activities of all compounds against the M. tuberculosis H37Rv strain were evaluated. Compound 3e exhibited a minimum inhibitory concentration in the micromolar range. Finally, Compound 3e showed no apparent toxicity in both HepG2 and Vero cells. The findings presented herein will advance the quest for novel, specific inhibitors targeting MtFolB, an attractive molecular target for TB drug development.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2388207"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11328599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975774","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

Bacillus lipopeptides inhibit lipase activity and promote 3T3-L1 preadipocyte differentiation. 芽孢杆菌脂肽抑制脂肪酶活性并促进 3T3-L1 前脂肪细胞分化

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: 10.1080/14756366.2024.2417915

Meichun Chen, Deju Chen, Rongfeng Xiao, Xuefang Zheng, Bo Liu, Jieping Wang

{"title":"Bacillus lipopeptides inhibit lipase activity and promote 3T3-L1 preadipocyte differentiation.","authors":"Meichun Chen, Deju Chen, Rongfeng Xiao, Xuefang Zheng, Bo Liu, Jieping Wang","doi":"10.1080/14756366.2024.2417915","DOIUrl":"10.1080/14756366.2024.2417915","url":null,"abstract":"Bacillus lipopeptides have been reported to display anti-obesity effects. In the present study, Lipopeptides from Bacillus velezensis FJAT-45028 that consisted of iturin, fengycin and surfactin were reported. The lipopeptides exhibited a strong lipase inhibition activity in a concentration-dependent manner with a half maximal inhibitory concentration of 0.012 mg/mL, and the inhibition mechanism and type were reversible and competitive, respectively. Results of CCK8 assay showed that 3T3-L1 preadipocyte cells were completely viable under treatment of 0.050-0.2 mg/mL lipopeptides for 24 or 48 h. It was found that the lipopeptides could increase lipid droplets in the differentiated 3T3-L1 adipocytes in tested concentration and suppress the expression of peroxisome proliferator-activated receptor gamma (PPARγ). These results indicated the potential anti-obesity mechanism of the tested lipopeptides might be to inhibit lipase activity but not to suppress lipid accumulation in the adipocytes. Moreover, the lipopeptides could elevate glucose utilisation by 14.43%-33.81% in the differentiated 3T3-L1 adipocytes.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2417915"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11497581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467262","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-guided discovery of novel dUTPase inhibitors with anti-Nocardia activity by computational design. 通过计算设计，在结构指导下发现具有抗诺卡氏菌活性的新型 dUTP 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: 2024-10-10 DOI: 10.1080/14756366.2024.2411573

Zhi-Zheng Wang, Jun Weng, Jing Qi, Xin-Xin Fu, Ban-Bin Xing, Yang Hu, Chun-Hsiang Huang, Chin-Yu Chen, Zigong Wei

{"title":"Structure-guided discovery of novel dUTPase inhibitors with anti-Nocardia activity by computational design.","authors":"Zhi-Zheng Wang, Jun Weng, Jing Qi, Xin-Xin Fu, Ban-Bin Xing, Yang Hu, Chun-Hsiang Huang, Chin-Yu Chen, Zigong Wei","doi":"10.1080/14756366.2024.2411573","DOIUrl":"10.1080/14756366.2024.2411573","url":null,"abstract":"The zoonosis caused by Nocardia is increasing seriously. But commonly used antibiotic drugs often lead to resistance. N. seriolae dUTPase (NsdUTPase) plays a key role in the proliferation of Nocardia, and was regarded as a potent drug target. However, there was little report about the NsdUTPase inhibitors. In this study, we discovered a series of novel NsdUTPase inhibitors to fight against Nocardia. The first crystal structure of NsdUTPase was released, and a structure-based computational design was performed. Compounds 4b and 12b exhibited promising activities towards NsdUTPase (IC50 = 0.99 μM and 0.7 μM). In addition, they showed satisfied anti-Nocardia activity (MIC value ranges from 0.5 to 2 mg/L) and low cytotoxicity, which were better than approved drugs oxytetracycline and florfenicol. Molecular modelling study indicated that hydrophobic interaction might be the main contribution for ligand binding. Our results suggested that NsdUTPase inhibitors might be a useful way to repress Nocardia.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2411573"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11486130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400472","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 multidisciplinary approach to the antioxidant and hepatoprotective activities of Arbutus pavarii Pampan fruit; in vitro and in Vivo biological evaluations, and in silico investigations. 采用多学科方法研究熊果的抗氧化和保肝活性；体外和体内生物评估以及硅学研究。

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: 10.1080/14756366.2023.2293639

Fatma A Elshibani, Abdullah D Alamami, Hamdoon A Mohammed, Rabab Ahmed Rasheed, Radwa M El Sabban, Mohamed A Yehia, Sherif S Abdel Mageed, Taghreed A Majrashi, Eslam B Elkaeed, Mahmoud A El Hassab, Wagdy M Eldehna, Mohamed K El-Ashrey

{"title":"A multidisciplinary approach to the antioxidant and hepatoprotective activities of Arbutus pavarii Pampan fruit; in vitro and in Vivo biological evaluations, and in silico investigations.","authors":"Fatma A Elshibani, Abdullah D Alamami, Hamdoon A Mohammed, Rabab Ahmed Rasheed, Radwa M El Sabban, Mohamed A Yehia, Sherif S Abdel Mageed, Taghreed A Majrashi, Eslam B Elkaeed, Mahmoud A El Hassab, Wagdy M Eldehna, Mohamed K El-Ashrey","doi":"10.1080/14756366.2023.2293639","DOIUrl":"10.1080/14756366.2023.2293639","url":null,"abstract":"The Libyan Strawberry, Arbutus pavarii Pampan (ARB), is an endemic Jebel Akhdar plant used for traditional medicine. This study presents the antioxidant and hepatoprotective properties of ARB fruit-extract. ARB phytochemical analysis indicated the presence of 354.54 GAE and 36.2 RE of the phenolics and flavonoids. LC-MS analysis identified 35 compounds belonging to phenolic acids, procyanidins, and flavonoid glycosides. Gallic acid, procyanidin dimer B3, β-type procyanidin trimer C, and quercetin-3-O-glucoside were the major constituents of the plant extract. ARB administration to paracetamol (PAR)-intoxicated rats reduced serum ALT, AST, bilirubin, hepatic tissue MDA and proinflammatory markers; TNF-α and IL-6 with an increase in tissue GSH level and SOD activity. Histological and immunohistochemical studies revealed that ARB restored the liver histology and significantly reduced the tissue expression of caspase 3, IL-1B, and NF-KB in PAR-induced liver damage. Docking analysis disclosed good binding affinities of some compounds with XO, COX-1, 5-LOX, and PI3K.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2293639"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10763860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048862","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

Imparting aromaticity to 2-pyridone derivatives by O-alkylation resulted in new competitive and non-competitive PIM-1 kinase inhibitors with caspase-activated apoptosis. 通过 O-烷基化使 2-吡啶酮衍生物具有芳香性，从而产生了新的具有竞争性和非竞争性的 PIM-1 激酶抑制剂，可激活 Caspase 使细胞凋亡。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-01-17 DOI: 10.1080/14756366.2024.2304044

Marwa E Abdelaziz, Mostafa M M El-Miligy, Salwa M Fahmy, Marwa M Abu-Serie, Aly A Hazzaa, Mona A Mahran

{"title":"Imparting aromaticity to 2-pyridone derivatives by O-alkylation resulted in new competitive and non-competitive PIM-1 kinase inhibitors with caspase-activated apoptosis.","authors":"Marwa E Abdelaziz, Mostafa M M El-Miligy, Salwa M Fahmy, Marwa M Abu-Serie, Aly A Hazzaa, Mona A Mahran","doi":"10.1080/14756366.2024.2304044","DOIUrl":"10.1080/14756366.2024.2304044","url":null,"abstract":"New aromatic O-alkyl pyridine derivatives were designed and synthesised as Proviral Integration Moloney (PIM)-1 kinase inhibitors. 4c and 4f showed potent in vitro anticancer activity against NFS-60, HepG-2, PC-3, and Caco-2 cell lines and low toxicity against normal human lung fibroblast Wi-38 cell line. Moreover, 4c and 4f induced apoptosis in the four tested cancer cell lines with high percentage. In addition, 4c and 4f significantly induced caspase 3/7 activation in HepG-2 cell line. Furthermore, 4c and 4f showed potent PIM-1 kinase inhibitory activity with IC50 = 0.110, 0.095 µM, respectively. Kinetic studies indicated that 4c and 4f were both competitive and non-competitive inhibitors for PIM-1 kinase enzyme. In addition, in silico prediction of physiochemical properties, pharmacokinetic profile, ligand efficiency, ligand lipophilic efficiency, and induced fit docking studies were consistent with the biological and kinetic studies, and predicted that 4c and 4f could act as PIM-1 kinase competitive non-adenosine triphosphate (ATP) mimetics with drug like properties.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2304044"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10795791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139478512","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, molecular modelling and biological evaluation of novel 6-amino-5-cyano-2-thiopyrimidine derivatives as potent anticancer agents against leukemia and apoptotic inducers. 新型 6-氨基-5-氰基-2-噻吩嘧啶衍生物的设计、合成、分子建模和生物学评价，作为抗白血病的强效抗癌剂和细胞凋亡诱导剂。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-02-13 DOI: 10.1080/14756366.2024.2304625

Naglaa M Ahmed, Mosaad S Mohamed, Samir M Awad, Rania H Abd El-Hameed, Neama A Abd El-Tawab, Mohamed S Gaballah, Ahmed M Said

{"title":"Design, synthesis, molecular modelling and biological evaluation of novel 6-amino-5-cyano-2-thiopyrimidine derivatives as potent anticancer agents against leukemia and apoptotic inducers.","authors":"Naglaa M Ahmed, Mosaad S Mohamed, Samir M Awad, Rania H Abd El-Hameed, Neama A Abd El-Tawab, Mohamed S Gaballah, Ahmed M Said","doi":"10.1080/14756366.2024.2304625","DOIUrl":"10.1080/14756366.2024.2304625","url":null,"abstract":"Herein, a novel series of 6-amino-5-cyano-2-thiopyrimidines and condensed pyrimidines analogues were prepared. All the synthesized compounds (1a-c, 2a-c, 3a-c, 4a-r and 5a-c) were evaluated for in vitro anticancer activity by the National Cancer Institute (NCI; MD, USA) against 60 cell lines. Compound 1c showed promising anticancer activity and was selected for the five-dose testing. Results demonstrated that compound 1c possessed broad spectrum anti-cancer activity against the nine cancerous subpanels tested with selectivity ratio ranging from 0.7 to 39 at the GI50 level with high selectivity towards leukaemia. Mechanistic studies showed that Compound 1c showed comparable activity to Duvelisib against PI3Kδ (IC50 = 0.0034 and 0.0025 μM, respectively) and arrested cell cycle at the S phase and displayed significant increase in the early and late apoptosis in HL60 and leukaemia SR cells. The necrosis percentage showed a significant increase from 1.13% to 3.41% in compound 1c treated HL60 cells as well as from 1.51% to 4.72% in compound 1c treated leukaemia SR cells. Also, compound 1c triggered apoptosis by activating caspase 3, Bax, P53 and suppressing Bcl2. Moreover, 1c revealed a good safety profile against human normal lung fibroblast cell line (WI-38 cells). Molecular analysis of Duvelisib and compound 1c in PI3K was performed. Finally, these results suggest that 2-thiopyrimidine derivative 1c might serve as a model for designing novel anticancer drugs in the future.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2304625"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10866072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722892","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

New natural protein tyrosine phosphatase 1B inhibitors from Gynostemma pentaphyllum. 从绞股蓝中提取的新型天然蛋白酪氨酸磷酸酶 1B 抑制剂。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-06-14 DOI: 10.1080/14756366.2024.2360063

Xianting Wang, Yidan Deng, Jianmei Wang, Lin Qin, Yimei Du, Qianru Zhang, Di Wu, Xingdong Wu, Jian Xie, Yuqi He, Daopeng Tan

{"title":"New natural protein tyrosine phosphatase 1B inhibitors from Gynostemma pentaphyllum.","authors":"Xianting Wang, Yidan Deng, Jianmei Wang, Lin Qin, Yimei Du, Qianru Zhang, Di Wu, Xingdong Wu, Jian Xie, Yuqi He, Daopeng Tan","doi":"10.1080/14756366.2024.2360063","DOIUrl":"10.1080/14756366.2024.2360063","url":null,"abstract":"Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease mainly caused by insulin resistance, which can lead to a series of complications such as cardiovascular disease, retinopathy, and its typical clinical symptom is hyperglycaemia. Glucosidase inhibitors, including Acarbose, Miglitol, are commonly used in the clinical treatment of hypoglycaemia. In addition, Protein tyrosine phosphatase 1B (PTP1B) is also an important promising target for the treatment of T2DM. Gynostemma pentaphyllum is a well-known oriental traditional medicinal herbal plant, and has many beneficial effects on glucose and lipid metabolism. In the present study, three new and nine known dammarane triterpenoids isolated from G. pentaphyllum, and their structures were elucidated by spectroscopic methods including HR-ESI-MS,1H and 13C NMR and X-ray crystallography. All these compounds were evaluated for inhibitory activity against α-glucosidase, α-amylase and PTP1B. The results suggested that compounds 7∼10 were potential antidiabetic agents with significantly inhibition activity against PTP1B in a dose-dependent manner.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2360063"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11182071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317384","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}

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