Perspectives in medicinal chemistry最新文献

The Structure-Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation. 经典大麻素的结构-功能关系：CB1/CB2 调节。

Perspectives in medicinal chemistry Pub Date : 2016-06-28 eCollection Date: 2016-01-01 DOI: 10.4137/PMC.S32171

Eric W Bow, John M Rimoldi

引用次数: 0

Interfering with Bacterial Quorum Sensing 干扰细菌群体感应

Perspectives in medicinal chemistry Pub Date : 2016-01-18 DOI: 10.4137/PMC.S13209

K. Reuter, A. Steinbach, V. Helms

引用次数: 99

Applications of second-harmonic generation imaging microscopy in ovarian and breast cancer. 二次谐波成像显微镜在卵巢癌和乳腺癌中的应用。

Perspectives in medicinal chemistry Pub Date : 2015-04-16 eCollection Date: 2015-01-01 DOI: 10.4137/PMC.S13214

Karissa Tilbury, Paul J Campagnola

{"title":"Applications of second-harmonic generation imaging microscopy in ovarian and breast cancer.","authors":"Karissa Tilbury, Paul J Campagnola","doi":"10.4137/PMC.S13214","DOIUrl":"https://doi.org/10.4137/PMC.S13214","url":null,"abstract":"In this perspective, we discuss how the nonlinear optical technique of second-harmonic generation (SHG) microscopy has been used to greatly enhance our understanding of the tumor microenvironment (TME) of breast and ovarian cancer. Striking changes in collagen architecture are associated with these epithelial cancers, and SHG can image these changes with great sensitivity and specificity with submicrometer resolution. This information has not historically been exploited by pathologists but has the potential to enhance diagnostic and prognostic capabilities. We summarize the utility of image processing tools that analyze fiber morphology in SHG images of breast and ovarian cancer in human tissues and animal models. We also describe methods that exploit the SHG physical underpinnings that are effective in delineating normal and malignant tissues. First we describe the use of polarization-resolved SHG that yields metrics related to macromolecular and supramolecular structures. The coherence and corresponding phase-matching process of SHG results in emission directionality (forward to backward), which is related to sub-resolution fibrillar assembly. These analyses are more general and more broadly applicable than purely morphology-based analyses; however, they are more computationally intensive. Intravital imaging techniques are also emerging that incorporate all of these quantitative analyses. Now, all these techniques can be coupled with rapidly advancing miniaturization of imaging systems to afford their use in clinical situations including enhancing pathology analysis and also in assisting in real-time surgical determination of tumor margins. ","PeriodicalId":88294,"journal":{"name":"Perspectives in medicinal chemistry","volume":"7 ","pages":"21-32"},"PeriodicalIF":0.0,"publicationDate":"2015-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/PMC.S13214","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33190376","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: 70

Selective Mycobacterium tuberculosis Shikimate Kinase Inhibitors as Potential Antibacterials. 选择性结核分枝杆菌莽草酸激酶抑制剂作为潜在的抗菌药物。

Perspectives in medicinal chemistry Pub Date : 2015-03-15 eCollection Date: 2015-01-01 DOI: 10.4137/PMC.S13212

Sara Gordon, Johayra Simithy, Douglas C Goodwin, Angela I Calderón

引用次数: 20

New approaches to treating Alzheimer's disease. 治疗阿尔茨海默病的新方法。

Perspectives in medicinal chemistry Pub Date : 2015-02-09 eCollection Date: 2015-01-01 DOI: 10.4137/PMC.S13210

Hailin Zheng, Mati Fridkin, Moussa Youdim

{"title":"New approaches to treating Alzheimer's disease.","authors":"Hailin Zheng, Mati Fridkin, Moussa Youdim","doi":"10.4137/PMC.S13210","DOIUrl":"https://doi.org/10.4137/PMC.S13210","url":null,"abstract":"To date, no truly efficacious drugs for Alzheimer's disease (AD) have been developed; moreover, all new anti-AD drugs developed since 2003 have failed. To succeed where previous ones have failed in drug development, new approaches for AD therapy are needed. Here we discuss the potential application of network medicine as a new approach to AD treatment. Unlike traditional approaches focused on a single target/pathway, network medicine targets and restores disease-disrupted networks through simultaneous modulation of numerous proteins (targets)/pathways involved in AD pathogenesis. We consider several drug candidates under development for AD therapy, including Keap1-Nrf2 regulators, endogenous neurogenic agents, and hypoxia-inducible factor 1 (HIF-1) activators. These drug candidates are multi-target ligands with the potential to further develop as network medicines, since they act as master regulators to initiate a broad range of cellular defense mechanisms/cytoprotective genes that exert their efficacy in a holistic way. We also explore their diverse mechanisms of action and potential disease-modifying effects, which may have profound implications for drug discovery. ","PeriodicalId":88294,"journal":{"name":"Perspectives in medicinal chemistry","volume":"7 ","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2015-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/PMC.S13210","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33097549","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: 39

Antimicrobial peptides and their analogs: searching for new potential therapeutics. 抗菌肽及其类似物：寻找新的潜在疗法。

Perspectives in medicinal chemistry Pub Date : 2014-10-12 eCollection Date: 2014-01-01 DOI: 10.4137/PMC.S13215

Krystyna Midura-Nowaczek, Agnieszka Markowska

引用次数: 0

Multiple sclerosis: overview of disease-modifying agents. 多发性硬化症:疾病调节剂的概述。

Perspectives in medicinal chemistry Pub Date : 2014-10-05 eCollection Date: 2014-01-01 DOI: 10.4137/PMC.S13213

Alessandro Finkelsztejn

引用次数: 45

Antibiotics and bacterial resistance in the 21st century. 21世纪的抗生素和细菌耐药性。

Perspectives in medicinal chemistry Pub Date : 2014-08-28 eCollection Date: 2014-01-01 DOI: 10.4137/PMC.S14459

Richard J Fair, Yitzhak Tor

引用次数: 1483

Pathways for small molecule delivery to the central nervous system across the blood-brain barrier. 通过血脑屏障向中枢神经系统输送小分子的途径。

Perspectives in medicinal chemistry Pub Date : 2014-06-16 eCollection Date: 2014-01-01 DOI: 10.4137/PMC.S13384

John L Mikitsh, Ann-Marie Chacko

{"title":"Pathways for small molecule delivery to the central nervous system across the blood-brain barrier.","authors":"John L Mikitsh, Ann-Marie Chacko","doi":"10.4137/PMC.S13384","DOIUrl":"10.4137/PMC.S13384","url":null,"abstract":"The treatment of central nervous system (CNS) disease has long been difficult due to the ineffectiveness of drug delivery across the blood-brain barrier (BBB). This review summarizes important concepts of the BBB in normal versus pathophysiology and how this physical, enzymatic, and efflux barrier provides necessary protection to the CNS during drug delivery, and consequently treatment challenging. Small molecules account for the vast majority of available CNS drugs primarily due to their ability to penetrate the phospholipid membrane of the BBB by passive or carrier-mediated mechanisms. Physiochemical and biological factors relevant for designing small molecules with optimal capabilities for BBB permeability are discussed, as well as the most promising classes of transporters suitable for small-molecule drug delivery. Clinically translatable imaging methodologies for detecting and quantifying drug uptake and targeting in the brain are discussed as a means of further understanding and refining delivery parameters for both drugs and imaging probes in preclinical and clinical domains. This information can be used as a guide to design drugs with preserved drug action and better delivery profiles for improved treatment outcomes over existing therapeutic approaches. ","PeriodicalId":88294,"journal":{"name":"Perspectives in medicinal chemistry","volume":"6 ","pages":"11-24"},"PeriodicalIF":0.0,"publicationDate":"2014-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32452209","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

Revisiting the monoamine hypothesis of depression: a new perspective. 重新审视抑郁症的单胺假说:一个新的视角。

Perspectives in medicinal chemistry Pub Date : 2014-04-03 eCollection Date: 2014-01-01 DOI: 10.4137/PMC.S11375

Joel S Goldberg, Clifton E Bell, David A Pollard

{"title":"Revisiting the monoamine hypothesis of depression: a new perspective.","authors":"Joel S Goldberg, Clifton E Bell, David A Pollard","doi":"10.4137/PMC.S11375","DOIUrl":"https://doi.org/10.4137/PMC.S11375","url":null,"abstract":"As the incidence of depression increases, depression continues to inflict additional suffering to individuals and societies and better therapies are needed. Based on magnetic resonance spectroscopy and laboratory findings, gamma aminobutyric acid (GABA) may be intimately involved in the pathophysiology of depression. The isoelectric point of GABA (pI = 7.3) closely approximates the pH of cerebral spinal fluid (CSF). This may not be a trivial observation as it may explain preliminary spectrophotometric, enzymatic, and HPLC data that monoamine oxidase (MAO) deaminates GABA. Although MAO is known to deaminate substrates such as catecholamines, indoleamines, and long chain aliphatic amines all of which contain a lipophilic moiety, there is very good evidence to predict that a low concentration of a very lipophilic microspecies of GABA is present when GABA pI = pH as in the CSF. Inhibiting deamination of this microspecies of GABA could explain the well-established successful treatment of refractory depression with MAO inhibitors (MAOI) when other antidepressants that target exclusively levels of monoamines fail. If further experimental work can confirm these preliminary findings, physicians may consider revisiting the use of MAOI for the treatment of non-intractable depression because the potential benefits of increasing GABA as well as the monoamines may outweigh the risks associated with MAOI therapy. ","PeriodicalId":88294,"journal":{"name":"Perspectives in medicinal chemistry","volume":"6 ","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2014-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/PMC.S11375","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32268503","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: 34