Abstract:
:Inosine 5'-monophosphate dehydrogenase (IMPDH) catalyzes the first committed step of guanosine 5'-monophosphate (GMP) biosynthesis, and thus regulates the guanine nucleotide pool, which in turn governs proliferation. Human IMPDHs are validated targets for immunosuppressive, antiviral and anticancer drugs, but as yet microbial IMPDHs have not been exploited in antimicrobial chemotherapy. Selective inhibitors of IMPDH from Cryptosporidium parvum have recently been discovered that display anti-parasitic activity in cell culture models of infection. X-ray crystal structure and mutagenesis experiments identified the structural features that determine inhibitor susceptibility. These features are found in IMPDHs from a wide variety of pathogenic bacteria, including select agents and multiply drug resistant strains. A second generation inhibitor displays antibacterial activity against Helicobacter pylori, demonstrating the antibiotic potential of IMPDH inhibitors.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Hedstrom L,Liechti G,Goldberg JB,Gollapalli DRdoi
10.2174/092986711795590129subject
Has Abstractpub_date
2011-01-01 00:00:00pages
1909-18issue
13eissn
0929-8673issn
1875-533Xpii
BSP/CMC/E-Pub/2011/ 134journal_volume
18pub_type
杂志文章,评审abstract::Drug repositioning, an innovative therapeutic application of an old drug, has received much attention as a particularly costeffective strategy in drug R&D Recent work has indicated that repositioning can be promoted by utilizing a wide range of information sources, including medicinal chemical, target, mechanism, main...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:
更新日期:2013-01-01 00:00:00
abstract::Trypanosomatids are a group of flagellated unicellular eukaryotes, causing serious human diseases including Chagas disease (Trypanosoma cruzi), sleeping sickness (Trypanosoma brucei spp.) and Leishmaniasis (Leishmania spp.). The second messenger cAMP is involved in numerous and fundamental processes in these parasites...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867326666190620093029
更新日期:2019-01-01 00:00:00
abstract::Cervical spondylotic myelopathy (CSM) is a very common and debilitating disease; however, its underlying pathocellular process remains uncertain. Attempts have been made to reproduce CSM in experimental animal models in order to deepen the knowledge on the molecular pathobiology of this disease. The up-to-date observa...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986710790820598
更新日期:2010-01-01 00:00:00
abstract::In the human brain several cell types are capable of initiating and amplifying a brain specific inflammatory response involving the synthesis of cytokines, prostaglandins and oxygen free radicals. In Alzheimer's disease (AD), signs of an inflammatory activation of microglia and astroglia are present inside and outside...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867023371292
更新日期:2002-01-01 00:00:00
abstract::Kinetoplastid and apicomplexan parasites comprise a group of protozoans responsible for human diseases, with a serious impact on human health and the socioeconomic growth of developing countries. Chemotherapy is the main option to control these pathogenic organisms and nucleotide metabolism is considered a promising a...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867325666180926154329
更新日期:2019-01-01 00:00:00
abstract::Angiotensin converting enzyme (ACE) 2 is a homologue of ACE that catalyzes the conversion of Angiotensin (Ang) II into Ang1-7, which induces vasodilation, anti-fibrotic, anti-proliferative and anti-inflammatory effects. Given that ACE2 counterbalances the effects of Ang II, it has been proposed as a biomarker in kidne...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170414162841
更新日期:2017-01-01 00:00:00
abstract::In recent years several mutations and sequence polymorphisms of the glucocorticoid receptor gene have been described. The majority of mutations have been found in patients with a rare endocrinological abnormality, the glucocorticoid resistance syndrome. In addition, some sequence polymorphisms have been considered to ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867043363749
更新日期:2004-12-01 00:00:00
abstract::The emergence of bacterial strains with resistance to currently marketed antibacterial agents has spurred interest in the discovery of new antibacterial agents with novel modes of action. One set of potential novel targets are the family of bacterial aminoacyltRNA synthetases (AaRS). Aminoacyl-tRNA synthetases are the...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986712801323199
更新日期:2012-01-01 00:00:00
abstract::The transport of organic and inorganic molecules, along with inorganic ions across the plasma membrane results in chemical fluxes that reflect the cellular function in healthy and diseased states. Measurement of these chemical fluxes enables the characterization of protein function and transporter stoichiometry, chara...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/0929867326666190506111629
更新日期:2019-05-06 00:00:00
abstract::The inhibition of protein degradation through the ubiquitin-proteasome pathway is a recently developed approach to cancer treatment which extends the range of cellular targets for chemotherapy. This therapeutic strategy is very interesting since the proteasomes carry out the regulated degradation of unnecessary or dam...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986708786848622
更新日期:2008-01-01 00:00:00
abstract::Recent advances have identified the podocyte as a key target in glomerular injury. The podocyte is a highly specialized cell which is responsible for the glomerular permselectivity for proteins in the kidney. Podocyte injury or loss leads to proteinuria. Apoptosis has been shown to contribute to renal cell loss, inclu...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986708784911542
更新日期:2008-01-01 00:00:00
abstract::Over the last decade there has been significant progress in understanding the molecular basis of disease processes. At the same time the technological advances in the area of genomics and the efforts in proteomics research have increased the possibility of discovering many proteins with defined therapeutic functions. ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986708785132924
更新日期:2008-01-01 00:00:00
abstract::Thymosin Beta-4 (Tβ4) is known as a major pleiotropic actin-sequestering protein that is involved in tumorigenesis. Tβ4 is a water-soluble protein that has different promising clinical applications in the remodeling and ulcerated tissues repair following myocardial infarction, stroke, plasticity and neurovascular remo...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867326666190716125456
更新日期:2020-01-01 00:00:00
abstract::Bone pain arising from secondary skeletal malignancy constitutes one of the most common types of chronic pain among patients with cancer which can lead to rapid deterioration of the quality of life. Radionuclide therapy using bone-seeking radiopharmaceuticals based on the concept of localization of the agent at bone m...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867326666190201142814
更新日期:2020-01-01 00:00:00
abstract::Substituted 2-arylbenzothiazoles have emerged in recent years as an important pharmacophore in a number of diagnostic and therapeutic settings. Attractive features of drug candidates based on this benzothiazole scaffold include their synthetic accessibility, and synthetic approaches to 2-arylbenzothiazole-based compou...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986709788682137
更新日期:2009-01-01 00:00:00
abstract::The study of iron chelators as anti-tumor agents is still in its infancy. Iron is important for cellular proliferation and this is demonstrated by observations that iron-depletion results in cell cycle arrest and also apoptosis. In addition, many iron chelators are known to inhibit ribonucleotide reductase, the iron-c...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986712800609706
更新日期:2012-01-01 00:00:00
abstract::The main challenge of cancer treatment is multidrug resistance during chemotherapy. Cancer cell can evade cell death during every round of orthodox chemotherapy drugs, consequently being resistant after several rounds of standard drug treatment. One of the regimens to address this multidrug resistance problem is by dr...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170920161922
更新日期:2018-01-01 00:00:00
abstract::Antibiotics play an irreplaceable role in the prevention and treatment of bacterial infection diseases. However, because of the improper use of antibiotics, bacterial resistance emerges as a major challenge of public health all over the world. The small thiol molecules such as glutathione can directly react and conjug...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/0929867326666190524125232
更新日期:2020-01-01 00:00:00
abstract::Antimitotics binding at the colchicine site of tubulin are important antitumour and vascular disrupting agents. Pyridines and azines are privileged scaffolds in medicinal chemistry and in recent years many colchicine site ligands (CSL) have incorporated them into their structures with the aim of improving their pharma...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986732311160420104823
更新日期:2016-01-01 00:00:00
abstract::Although resin-based chemistry offers many practical advantages over conventional solution phase for the synthesis of combinatorial libraries, effective monitoring of reactions conducted on the support remains a challenge. A number of techniques have been developed to enable the analysis of solid phase organic synthes...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867023368737
更新日期:2002-12-01 00:00:00
abstract:BACKGROUND:Monocyte chemoattractant protein-1 (MCP-1) is a member of the CC chemokine family that plays a key role in the inflammatory process. It has been broadly studied in the aspect of its role in obesity and diabetes related diseases. MCP-1 causes the infiltration of macrophages into obese adipose tissue via bindi...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170303162935
更新日期:2017-01-01 00:00:00
abstract::Coumarins, also referred as benzopyran-2-ones, and their corresponding nitrogen counterpart, 1-azacoumarins also referred to as carbostyrils, are a family of nature-occurring lactones and lactams respectively. The plant extracts containing coumarin-related heterocycles, which were employed as herbal remedies in early ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986706778521968
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:Immunomodulation is one of the significant therapeutic strategies. It includes both stimulation and suppression of the immune system by a variety of substances called immunomodulators, designed to regulate the immune response of the organism against infections of varying etiology. An example of such a substa...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170725140826
更新日期:2017-11-17 00:00:00
abstract::Fabry disease (FD) is an X-linked glycosphingolipid storage disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A. This leads to a progressive accumulation of globotriaosylceramide (Gb3) in the lysosomes of different cells and tissues, causing principally ventricular hypertrophy, renal fa...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986710791111297
更新日期:2010-01-01 00:00:00
abstract::The transport mechanisms of ascorbic acid (AA) are described. The metabolism of AA and its function as an antioxidant are covered in some detail. Subsequently, indications for postoperative substitution are discussed. The supplementation of up to 300 mg of AA per day in postoperative intensive care unit patients durin...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986709787002781
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:Inflammation is one of the most misunderstood aspects of human health. People have been encouraged to eat foods that have a high antioxidant capacity, and in vitro tests for total antioxidant capacity emerged. They were based on measuring the destruction of oxidized test compounds in direct reactions with th...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867326666190517113533
更新日期:2020-01-01 00:00:00
abstract::alpha-Galactosylceramide (alpha-GalCer), is a glycolipid which has been identified as a ligand recognized by a special group of immune T cells, known as invariant NKT cells. alpha-GalCer can powerfully activate invariant NKT cells to produce immunoregulatory cytokines, including interferon-gamma and IL-4, and thereby ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867043456115
更新日期:2004-01-01 00:00:00
abstract::Complete DNA sequence information has now been obtained for several prokaryotic genomes, defining the entire genetic complement of these organisms. The collection of genomic data has provided new insights into the molecular architecture of bacterial cells, revealing the basic genetic and metabolic structures that supp...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867013371699
更新日期:2001-12-01 00:00:00
abstract::Matrix metalloproteinases (MMPs) are essential for the degradation and turnover of components of the extracellular matrix (ECM) and, when pathologically elevated, mediate connective tissue loss (including bone destruction) in various inflammatory and other diseases. Tetracyclines (TCs) are known inhibitors of mammalia...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/092986712802884295
更新日期:2012-01-01 00:00:00
abstract::Molecules in biological systems often can perform more than one function. In particular, many molecules have the ability to chemically scavenge free radicals and thus act in the test tube as antioxidant, but their main biological function is by acting as hormones, ligands for transcription factors, modulators of enzym...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867043365332
更新日期:2004-05-01 00:00:00