Journal of Chemical Biology最新文献_第6页

Identification of a new pharmacological activity of the phenylpiperazine derivative naftopidil: tubulin-binding drug. 苯哌嗪衍生物萘托地尔的新药理活性鉴定:微管蛋白结合药物。

Journal of Chemical Biology Pub Date : 2014-09-06 eCollection Date: 2015-01-01 DOI: 10.1007/s12154-014-0122-0

Kenichiro Ishii, Yoshiki Sugimura

{"title":"Identification of a new pharmacological activity of the phenylpiperazine derivative naftopidil: tubulin-binding drug.","authors":"Kenichiro Ishii, Yoshiki Sugimura","doi":"10.1007/s12154-014-0122-0","DOIUrl":"https://doi.org/10.1007/s12154-014-0122-0","url":null,"abstract":"The phenylpiperazine derivative naftopidil is an α1-adrenoceptor (AR) antagonist that has been used clinically to treat benign prostatic hyperplasia. In our drug repositioning research, naftopidil shows the unique growth-inhibitory effects. Naftopidil inhibits cell cycle progression not only in cancer cells, but also in fibroblasts and vascular endothelial cells. Naftopidil-inhibited cell cycle progression is independent of α1-AR expression in cells. Therefore, the antiproliferative effects of naftopidil may be due to the off-target effects of the drug. In this study, we attempted to identify the off-target molecules of naftopidil using the magnetic nanobeads, ferrite glycidyl metharcrylate (FG) beads. Similar to naftopidil, its derivatives TG09-01 and TG09-02, which were introduced with amino groups for immobilizing to FG beads, inhibited cell growth in human HT29 colon adenocarcinoma cells. Both derivatives were associated with inhibition of cell cycle progression in HT29 cells. This observation is consistent with that seen with naftopidil. Using TG09-02-immobilized FG beads, α- and β-tubulins were identified as the specific binding proteins of naftopidil. The tubulin polymerization assay clearly indicated that naftopidil bound directly to tubulin and inhibited the polymerization of tubulin. Other phenylpiperazine derivatives, such as RS100329, BMY7378, and KN-62, also inhibited the polymerization of tubulin. These results suggest that phenylpiperazine derivatives including naftopidil may have broad spectrum of cellular cytotoxicity in various types of cells. In addition, the tubulin polymerization-inhibiting activity of phenylpiperazine derivatives may be a specific feature of the phenylpiperazine-based structure. These findings can allow us to design and synthesize new tubulin-binding drugs derived from naftopidil as a lead compound. ","PeriodicalId":15296,"journal":{"name":"Journal of Chemical Biology","volume":"8 1","pages":"5-9"},"PeriodicalIF":0.0,"publicationDate":"2014-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12154-014-0122-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32971167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 13

Resistance to antifungals that target CYP51. 对靶向CYP51的抗真菌药物的耐药性。

Journal of Chemical Biology Pub Date : 2014-08-27 eCollection Date: 2014-10-01 DOI: 10.1007/s12154-014-0121-1

Josie E Parker, Andrew G S Warrilow, Claire L Price, Jonathan G L Mullins, Diane E Kelly, Steven L Kelly

{"title":"Resistance to antifungals that target CYP51.","authors":"Josie E Parker, Andrew G S Warrilow, Claire L Price, Jonathan G L Mullins, Diane E Kelly, Steven L Kelly","doi":"10.1007/s12154-014-0121-1","DOIUrl":"https://doi.org/10.1007/s12154-014-0121-1","url":null,"abstract":"Fungal diseases are an increasing global burden. Fungi are now recognised to kill more people annually than malaria, whilst in agriculture, fungi threaten crop yields and food security. Azole resistance, mediated by several mechanisms including point mutations in the target enzyme (CYP51), is increasing through selection pressure as a result of widespread use of triazole fungicides in agriculture and triazole antifungal drugs in the clinic. Mutations similar to those seen in clinical isolates as long ago as the 1990s in Candida albicans and later in Aspergillus fumigatus have been identified in agriculturally important fungal species and also wider combinations of point mutations. Recently, evidence that mutations originate in the field and now appear in clinical infections has been suggested. This situation is likely to increase in prevalence as triazole fungicide use continues to rise. Here, we review the progress made in understanding azole resistance found amongst clinically and agriculturally important fungal species focussing on resistance mechanisms associated with CYP51. Biochemical characterisation of wild-type and mutant CYP51 enzymes through ligand binding studies and azole IC50 determinations is an important tool for understanding azole susceptibility and can be used in conjunction with microbiological methods (MIC50 values), molecular biological studies (site-directed mutagenesis) and protein modelling studies to inform future antifungal development with increased specificity for the target enzyme over the host homologue. ","PeriodicalId":15296,"journal":{"name":"Journal of Chemical Biology","volume":"7 4","pages":"143-61"},"PeriodicalIF":0.0,"publicationDate":"2014-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12154-014-0121-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32752053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 125

Biological and chemical approaches towards combating resistance in agriculture. 对抗农业抗性的生物和化学方法。

Journal of Chemical Biology Pub Date : 2014-08-12 eCollection Date: 2014-10-01 DOI: 10.1007/s12154-014-0120-2

Stephen Lindell, Stuart John Dunbar

引用次数: 0

EU-OPENSCREEN-chemical tools for the study of plant biology and resistance mechanisms. 欧盟- openscreen -用于研究植物生物学和抗性机制的化学工具。

Journal of Chemical Biology Pub Date : 2014-07-31 eCollection Date: 2014-10-01 DOI: 10.1007/s12154-014-0118-9

Torsten Meiners, Bahne Stechmann, Ronald Frank

{"title":"EU-OPENSCREEN-chemical tools for the study of plant biology and resistance mechanisms.","authors":"Torsten Meiners, Bahne Stechmann, Ronald Frank","doi":"10.1007/s12154-014-0118-9","DOIUrl":"https://doi.org/10.1007/s12154-014-0118-9","url":null,"abstract":"EU-OPENSCREEN is an academic research infrastructure initiative in Europe for enabling researchers in all life sciences to take advantage of chemical biology approaches to their projects. In a collaborative effort of national networks in 16 European countries, EU-OPENSCREEN will develop novel chemical compounds with external users to address questions in, among other fields, systems and network biology (directed and selective perturbation of signalling pathways), structural biology (compound-target interactions at atomic resolution), pharmacology (early drug discovery and toxicology) and plant biology (response of wild or crop plants to environmental and agricultural substances). EU-OPENSCREEN supports all stages of a tool development project, including assay adaptation, high-throughput screening and chemical optimisation of the 'hit' compounds. All tool compounds and data will be made available to the scientific community. EU-OPENSCREEN integrates high-capacity screening platforms throughout Europe, which share a rationally selected compound collection comprising up to 300,000 (commercial and proprietary compounds collected from European chemists). By testing systematically this chemical collection in hundreds of assays originating from very different biological themes, the screening process generates enormous amounts of information about the biological activities of the substances and thereby steadily enriches our understanding of how and where they act. ","PeriodicalId":15296,"journal":{"name":"Journal of Chemical Biology","volume":"7 4","pages":"113-8"},"PeriodicalIF":0.0,"publicationDate":"2014-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12154-014-0118-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32752047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Herbicide resistance-what have we learned from other disciplines? 除草剂抗性——我们从其他学科中学到了什么?

Journal of Chemical Biology Pub Date : 2014-07-30 eCollection Date: 2014-10-01 DOI: 10.1007/s12154-014-0119-8

Harry J Strek

引用次数: 8

The physical influence of inositides-a disproportionate effect? 肌醇对身体的影响——不成比例的影响?

Journal of Chemical Biology Pub Date : 2014-07-20 eCollection Date: 2015-01-01 DOI: 10.1007/s12154-014-0117-x

Samuel Furse

引用次数: 8

Target-site resistance to neonicotinoids. 靶点对新烟碱类的抗性。

Journal of Chemical Biology Pub Date : 2014-07-17 eCollection Date: 2014-10-01 DOI: 10.1007/s12154-014-0116-y

Andrew J Crossthwaite, Stefano Rendine, Marco Stenta, Russell Slater

引用次数: 39

JOCB Bulletin. JOCB公告。

Journal of Chemical Biology Pub Date : 2014-06-22 eCollection Date: 2014-07-01 DOI: 10.1007/s12154-014-0114-0

引用次数: 0

Synthesis, molecular docking and antibacterial evaluation of new 1,4-naphthoquinone derivatives contains carbazole-6,11-dione moiety. 含有咔唑-6,11-二酮的1,4-萘醌衍生物的合成、分子对接及抗菌性能评价。

Journal of Chemical Biology Pub Date : 2014-06-12 eCollection Date: 2014-07-01 DOI: 10.1007/s12154-014-0115-z

P Ravichandiran, D Premnath, S Vasanthkumar

{"title":"Synthesis, molecular docking and antibacterial evaluation of new 1,4-naphthoquinone derivatives contains carbazole-6,11-dione moiety.","authors":"P Ravichandiran, D Premnath, S Vasanthkumar","doi":"10.1007/s12154-014-0115-z","DOIUrl":"https://doi.org/10.1007/s12154-014-0115-z","url":null,"abstract":"A new series of new 1,4-naphthoquinone derivatives containing carbazole-6,11-dione moiety, which has not been reported yet, has been synthesized from 1,4-naphthoquinone and 4-aminophenylsulfone involving a Michael addition, benzoylation, and Pd-catalyzed coupling. This set of compounds has been evaluated for in vitro antibacterial studies against different Gram-positive and Gram-negative bacteria, and most of the synthesized compounds exhibited good antibacterial activity and the minimum inhibitory concentrations (MICs) are compared with the standard drugs used. Compound 7 exhibited good antibacterial activity among all the molecules studied with the best MIC of 2.1 μg/mL against Bacillus subtilis. To understand the molecular interactions with targeted proteins, the molecular docking of all the synthesized compounds were carried out; between 14 molecules docked, compound 7 was the one with the best glide and E model score of -7.73 and -95.37, respectively. In all docked molecules, compound 5 exhibited least glide and E model score of -4.55 and -101.56, respectively. Figureᅟ ","PeriodicalId":15296,"journal":{"name":"Journal of Chemical Biology","volume":"7 3","pages":"93-101"},"PeriodicalIF":0.0,"publicationDate":"2014-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12154-014-0115-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32546242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

The rising threat of fungicide resistance in plant pathogenic fungi: Botrytis as a case study. 植物病原真菌对杀真菌剂产生抗药性的威胁日益严重：以灰霉病为例。

Journal of Chemical Biology Pub Date : 2014-05-28 eCollection Date: 2014-10-01 DOI: 10.1007/s12154-014-0113-1

Matthias Hahn

{"title":"The rising threat of fungicide resistance in plant pathogenic fungi: Botrytis as a case study.","authors":"Matthias Hahn","doi":"10.1007/s12154-014-0113-1","DOIUrl":"10.1007/s12154-014-0113-1","url":null,"abstract":"The introduction of site-specific fungicides almost 50 years ago has revolutionized chemical plant protection, providing highly efficient, low toxicity compounds for control of fungal diseases. However, it was soon discovered that plant pathogenic fungi can adapt to fungicide treatments by mutations leading to resistance and loss of fungicide efficacy. The grey mould fungus Botrytis cinerea, a major cause of pre- and post-harvest losses in fruit and vegetable production, is notorious as a 'high risk' organism for rapid resistance development. In this review, the mechanisms and the history of fungicide resistance in Botrytis are outlined. The introduction of new fungicide classes for grey mould control was always followed by the appearance of resistance in field populations. In addition to target site resistance, B. cinerea has also developed a resistance mechanism based on drug efflux transport. Excessive spraying programmes have resulted in the selection of multiresistant strains in several countries, in particular in strawberry fields. The rapid erosion of fungicide activity against these strains represents a major challenge for the future of fungicides against Botrytis. To maintain adequate protection of intensive cultures against grey mould, strict implementation of resistance management measures are required as well as alternative strategies with non-chemical products. ","PeriodicalId":15296,"journal":{"name":"Journal of Chemical Biology","volume":"7 4","pages":"133-41"},"PeriodicalIF":0.0,"publicationDate":"2014-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182335/pdf/12154_2014_Article_113.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32752051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0