Pub Date : 2024-12-01Epub Date: 2023-12-21DOI: 10.1080/14756366.2023.2297117
{"title":"Correction.","authors":"","doi":"10.1080/14756366.2023.2297117","DOIUrl":"10.1080/14756366.2023.2297117","url":null,"abstract":"","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2297117"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10763826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138829972","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}
Pub Date : 2024-12-01Epub Date: 2024-07-25DOI: 10.1080/14756366.2024.2367129
Di Wang, Jiang-Jie Duan, Yu-Feng Guo, Jun-Jie Chen, Tian-Qing Chen, Jun Wang, Shi-Cang Yu
Metabolic abnormalities are an important feature of tumours. The glutamine-arginine-proline axis is an important node of cancer metabolism and plays a major role in amino acid metabolism. This axis also acts as a scaffold for the synthesis of other nonessential amino acids and essential metabolites. In this paper, we briefly review (1) the glutamine addiction exhibited by tumour cells with accelerated glutamine transport and metabolism; (2) the methods regulating extracellular glutamine entry, intracellular glutamine synthesis and the fate of intracellular glutamine; (3) the glutamine, proline and arginine metabolic pathways and their interaction; and (4) the research progress in tumour therapy targeting the glutamine-arginine-proline metabolic system, with a focus on summarising the therapeutic research progress of strategies targeting of one of the key enzymes of this metabolic system, P5CS (ALDH18A1). This review provides a new basis for treatments targeting the metabolic characteristics of tumours.
{"title":"Targeting the glutamine-arginine-proline metabolism axis in cancer.","authors":"Di Wang, Jiang-Jie Duan, Yu-Feng Guo, Jun-Jie Chen, Tian-Qing Chen, Jun Wang, Shi-Cang Yu","doi":"10.1080/14756366.2024.2367129","DOIUrl":"10.1080/14756366.2024.2367129","url":null,"abstract":"<p><p>Metabolic abnormalities are an important feature of tumours. The glutamine-arginine-proline axis is an important node of cancer metabolism and plays a major role in amino acid metabolism. This axis also acts as a scaffold for the synthesis of other nonessential amino acids and essential metabolites. In this paper, we briefly review (1) the glutamine addiction exhibited by tumour cells with accelerated glutamine transport and metabolism; (2) the methods regulating extracellular glutamine entry, intracellular glutamine synthesis and the fate of intracellular glutamine; (3) the glutamine, proline and arginine metabolic pathways and their interaction; and (4) the research progress in tumour therapy targeting the glutamine-arginine-proline metabolic system, with a focus on summarising the therapeutic research progress of strategies targeting of one of the key enzymes of this metabolic system, P5CS (ALDH18A1). This review provides a new basis for treatments targeting the metabolic characteristics of tumours.</p>","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2367129"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11275534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759105","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}
Pub Date : 2024-12-01Epub Date: 2024-02-07DOI: 10.1080/14756366.2024.2305856
Mohamed A Mahmoud, Anber F Mohammed, Ola I A Salem, Tahani Mazyad Almutairi, Stefan Bräse, Bahaa G M Youssif
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.
{"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":"<p><p>A novel series of 1,2,3-triazole/1,2,4-oxadiazole hybrids (<b>7a</b>-<b>o</b>) was developed as dual inhibitors of EGFR/VEGFR-2. Compounds <b>7a</b>-<b>o</b> were evaluated as antiproliferative agents with Erlotinib as the reference drug. Results demonstrated that most of the tested compounds showed significant antiproliferative action with GI<sub>50</sub> values ranging from 28 to 104 nM, compared to Erlotinib (GI<sub>50</sub> = 33 nM), and compounds <b>7i</b>-<b>m</b> were the most potent. Compounds <b>7h</b>, <b>7i</b>, <b>7j</b>, <b>7k</b>, and <b>7l</b> were evaluated as dual EGFR/VEGFR-2 inhibitors. These <i>in vitro</i> experiments demonstrated that compounds <b>7j</b>, <b>7k</b>, and <b>7l</b> are potent antiproliferative agents that may operate as dual EGFR/VEGFR-2 inhibitors. Compounds <b>7j</b>, <b>7k</b>, and <b>7l</b> were evaluated for their apoptotic potential activity, where findings indicated that compounds <b>7j</b>, <b>7k,</b> and <b>7l</b> 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.</p>","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}
Pub Date : 2024-12-01Epub Date: 2023-12-18DOI: 10.1080/14756366.2023.2296695
Mengru Jin, Luyao Shi, Li Wang, Dingyuan Zhang, Yanjing Li
Photodynamic therapy (PDT) has been demonstrated to provide immediate relief of oesophageal cancer patients' re-obstruction and extend their lifespan. However, tumour regrowth may occur after PDT due to enhanced aerobic glycolysis. Previous research has confirmed the inhibitory effect of Dihydroartemisinin (DHA) on aerobic glycolysis. Therefore, the current study intends to investigate the function and molecular mechanism of DHA targeting tumour cell aerobic glycolysis in synergia PDT. The combined treatment significantly suppressed glycolysis in vitro and in vivo compared to either monotherapy. Exploration of the mechanism through corresponding experiments revealed that pyruvate kinase M2 (PKM2) was downregulated in treated cells, whereas overexpression of PKM2 nullified the inhibitory effects of DHA and PDT. This study proposes a novel therapeutic strategy for oesophageal cancer through DHA-synergized PDT treatment, targeting inhibit PKM2 to reduce tumour cell proliferation and metastasis.
光动力疗法(PDT)已被证明能立即缓解食道癌患者的再梗阻,并延长他们的寿命。然而,由于有氧糖酵解作用增强,光动力疗法后可能会导致肿瘤再生。先前的研究证实了双氢青蒿素(DHA)对有氧糖酵解的抑制作用。因此,本研究旨在探讨 DHA 在协同 PDT 中靶向肿瘤细胞有氧糖酵解的功能和分子机制。与单一疗法相比,联合疗法能明显抑制体外和体内糖酵解。通过相应的实验探索其机制发现,丙酮酸激酶M2(PKM2)在治疗细胞中下调,而过表达PKM2则使DHA和PDT的抑制作用无效。本研究提出了一种新的食道癌治疗策略,即通过DHA协同PDT治疗,以抑制PKM2为靶点,减少肿瘤细胞的增殖和转移。
{"title":"Dihydroartemisinin enhances the anti-tumour effect of photodynamic therapy by targeting PKM2-mediated glycolysis in oesophageal cancer cell.","authors":"Mengru Jin, Luyao Shi, Li Wang, Dingyuan Zhang, Yanjing Li","doi":"10.1080/14756366.2023.2296695","DOIUrl":"10.1080/14756366.2023.2296695","url":null,"abstract":"<p><p>Photodynamic therapy (PDT) has been demonstrated to provide immediate relief of oesophageal cancer patients' re-obstruction and extend their lifespan. However, tumour regrowth may occur after PDT due to enhanced aerobic glycolysis. Previous research has confirmed the inhibitory effect of Dihydroartemisinin (DHA) on aerobic glycolysis. Therefore, the current study intends to investigate the function and molecular mechanism of DHA targeting tumour cell aerobic glycolysis in synergia PDT. The combined treatment significantly suppressed glycolysis in vitro and in vivo compared to either monotherapy. Exploration of the mechanism through corresponding experiments revealed that pyruvate kinase M2 (PKM2) was downregulated in treated cells, whereas overexpression of PKM2 nullified the inhibitory effects of DHA and PDT. This study proposes a novel therapeutic strategy for oesophageal cancer through DHA-synergized PDT treatment, targeting inhibit PKM2 to reduce tumour cell proliferation and metastasis.</p>","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2296695"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11722009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138804772","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}
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.
{"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":"<p><p>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.</p>","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}
Pub Date : 2024-12-01Epub Date: 2024-06-07DOI: 10.1080/14756366.2024.2351861
Ateyatallah Aljuhani, Mosa Alsehli, Mohamed A Seleem, Shaya Y Alraqa, Hany E A Ahmed, Nadjet Rezki, Mohamed R Aouad
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.
本研究设计、合成了一个与 1,4-二取代-1,2,3-三唑相连的邻苯二甲酰亚胺席夫碱库,并通过不同的光谱分析对其进行了表征。以 Vero 细胞为培养基,对所有类似物进行了体外试验,检测它们对不同浓度 COVID-19 病毒的抗病毒活性。数据显示,这些衍生物中的大多数都具有很强的细胞抗 COVID-19 活性,在两种不同浓度下可阻止 90% 以上的病毒生长,对 Vero 细胞无细胞毒性或细胞毒性很弱。此外,还对所有类似物进行了针对该酶的体外检测,结果显示其中两种类似物的 IC50 数据为 90 µM 抑制活性。为了分析它们的抗病毒机理,我们进行了广泛的分子对接模拟,发现它们在 Mpro 蛋白酶内有适当的非共价相互作用。最后,我们还发现了两种可逆抑制剂,即 COOH 和 F 取代的类似物,它们可能是有希望进一步开发的候选药物。
{"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":"<p><p>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 <i>in vitro</i> 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, <i>in vitro</i> 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.</p>","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}
Pub Date : 2024-12-01Epub Date: 2024-08-14DOI: 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
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.
研究人员阐明了结核分枝杆菌 FolB 酶(MtFolB)与其抑制剂 8-巯基鸟嘌呤(8-MG)复合物的晶体结构,其分辨率为 1.95 Å。合成了一系列新型 S8 功能化 8-MG 衍生物,并将其作为 MtFolB 的二氢酮蝶呤醛缩酶(DHNA,EC 4.1.2.25)活性的体外抑制剂进行了评估。这些化合物的 IC50 值在亚摩尔范围内。对五种化合物的活性评估表明了它们的抑制模式和抑制常数。通过分子对接分析确定了复合物形成时酶抑制剂分子间的相互作用和配体构象。评估了所有化合物对结核杆菌 H37Rv 株的抑制活性。化合物 3e 的最低抑制浓度在微摩尔范围内。最后,化合物 3e 对 HepG2 和 Vero 细胞均无明显毒性。本文介绍的研究结果将推动针对 MtFolB 的新型特异性抑制剂的开发,MtFolB 是结核病药物开发的一个极具吸引力的分子靶点。
{"title":"Crystal structure of dihydroneopterin aldolase from <i>Mycobacterium tuberculosis</i> associated with 8-mercaptoguanine, and development of novel S8-functionalized analogues as inhibitors: Synthesis, enzyme inhibition, <i>in vitro</i> 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":"<p><p>The crystallographic structure of the FolB enzyme from <i>Mycobacterium tuberculosis</i> (<i>Mt</i>FolB), 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 <i>in vitro</i> inhibitors of dihydroneopterin aldolase (DHNA, EC 4.1.2.25) activity of <i>Mt</i>FolB. These compounds exhibited IC<sub>50</sub> 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 <i>M. tuberculosis</i> H37Rv strain were evaluated. Compound <b>3e</b> exhibited a minimum inhibitory concentration in the micromolar range. Finally, Compound <b>3e</b> showed no apparent toxicity in both HepG2 and Vero cells. The findings presented herein will advance the quest for novel, specific inhibitors targeting <i>Mt</i>FolB, an attractive molecular target for TB drug development.</p>","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}
Pub Date : 2024-12-01Epub Date: 2024-10-21DOI: 10.1080/14756366.2024.2417915
Meichun Chen, Deju Chen, Rongfeng Xiao, Xuefang Zheng, Bo Liu, Jieping Wang
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.
{"title":"<i>Bacillus</i> 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":"<p><p><i>Bacillus</i> lipopeptides have been reported to display anti-obesity effects. In the present study, Lipopeptides from <i>Bacillus velezensis</i> 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.</p>","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}
Pub Date : 2024-12-01Epub Date: 2024-10-10DOI: 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
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.
{"title":"Structure-guided discovery of novel dUTPase inhibitors with anti-<i>Nocardia</i> 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":"<p><p>The zoonosis caused by <i>Nocardia</i> is increasing seriously. But commonly used antibiotic drugs often lead to resistance. <i>N. seriolae</i> dUTPase (<i>Ns</i>dUTPase) plays a key role in the proliferation of <i>Nocardia</i>, and was regarded as a potent drug target. However, there was little report about the <i>Ns</i>dUTPase inhibitors. In this study, we discovered a series of novel <i>Ns</i>dUTPase inhibitors to fight against <i>Nocardia</i>. The first crystal structure of <i>Ns</i>dUTPase was released, and a structure-based computational design was performed. Compounds <b>4b</b> and <b>12b</b> exhibited promising activities towards <i>Ns</i>dUTPase (IC<sub>50</sub> = 0.99 μM and 0.7 μM). In addition, they showed satisfied anti-<i>Nocardia</i> 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 <i>Ns</i>dUTPase inhibitors might be a useful way to repress <i>Nocardia</i>.</p>","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}
Pub Date : 2024-12-01Epub Date: 2023-12-28DOI: 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
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.
{"title":"A multidisciplinary approach to the antioxidant and hepatoprotective activities of <i>Arbutus pavarii</i> Pampan fruit; <i>in vitro</i> and <i>in Vivo</i> biological evaluations, and <i>in silico</i> 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":"<p><p>The Libyan Strawberry, <i>Arbutus pavarii</i> 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.</p>","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}