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New Lead Compounds (new + lead_compound)
Selected Abstracts3-Bromo-4-(1H-3-indolyl)-2,5-dihydro-1H-2,5-pyrroledione Derivatives as New Lead Compounds for Antibacterially Active Substances.CHEMINFORM, Issue 31 2006Siavosh Mahboobi Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Comparison of anti-inflammatory activities of ruscogenin, a major steroidal sapogenin from Radix Ophiopogon japonicus, and Its succinylated derivative, RUS-2HSDRUG DEVELOPMENT RESEARCH, Issue 4 2008Ya-Lin Huang Abstract Ruscogenin (RUS), first isolated from Ruscus aculeatus, is also a major steroidal sapogenin of the traditional Chinese herb Radix Ophiopogon japonicus. It has robust anti-inflammatory activities. In previous studies, a ruscogenin affinity column, derived from succinylated ruscogenin (RUS-2HS), was used to purify an antibody of ruscogenin. A ruscogenin affinity column can also be used to explore its protein targets. However, until now there have been no related pharmacological reports about ruscogenin derivatives. Whether the activity groups of ruscogenin have been blocked during the derivation process remains unknown. The present study was performed to compare the anti-inflammatory activities in vitro of RUS-2HS and ruscogenin. Both compounds reduced tumor necrosis factor-, (TNF-,)-induced adhesion of human pro-myelocytic leukemia cells (HL-60) to endothelial ECV304 cells with IC50 values of 6.90,nM and 7.45,nM, respectively. They were also inhibited overexpression of ICAM-1 in ECV304 cells at the mRNA level as evaluated by real-time PCR and at the protein level evaluated by flow cytometry with similar potency. Such data demonstrate that the functional groups of ruscogenin were not blocked by derivation, suggesting further use of the ruscogenin affinity column for target investigation. Meanwhile, RUS-2HS was found to have remarkable anti-inflammatory activity for the first time, indicating it would be a new lead compound with improved bioavailability. Drug Dev Res 69: 196,202, 2008. © 2008 Wiley-Liss, Inc. [source] Synthesis of a New Seleninic Acid Anhydride and Mechanistic Studies into Its Glutathione Peroxidase ActivityCHEMISTRY - A EUROPEAN JOURNAL, Issue 23 2008Sun-Chol Yu Dr. Abstract Starting from low toxic salicyloylglycine, a new seleninic acid anhydride 7 that lacks Se,,,N or Se,,,O non-bonded interactions was synthesized. This compound exhibits a fourfold higher glutathione peroxidase-like (GPx-like) activity than ebselen and inhibits plant and mammalian 12/15-lipoxygenases at lower micromolar concentrations. Because of these pharmacological properties, 7 may constitute a new lead compound for the development of anti-inflammatory low-molecular-weight seleno-organic compounds. Analyzing the redox products of 7 with glutathione (GSH) and tBuOOH, we identified three potential catalytic cycles (A, B, C) of GPx-like activity that are interconnected by key metabolites. To study the relative contribution of these cycles to the catalytic activity, we prepared selected reaction intermediates and found that the activity of seleninic acid anhydride 7 and of the corresponding diselenide 11 and selenol 14 compounds were in the same range. In contrast, the GPx-like activity of monoselenide 9 was more than one order of magnitude lower. These data suggested that cycles A and B may constitute the major routes of GPx-like activity of 7, whereas cycle C may not significantly contribute to catalysis. [source] Syringolin A, a new plant elicitor from the phytopathogenic bacterium Pseudomonas syringae pv. syringae, inhibits the proliferation of neuroblastoma and ovarian cancer cells and induces apoptosisCELL PROLIFERATION, Issue 6 2006C. S. Coleman The goal of this study was to investigate whether syringolin A exhibits anti-proliferative properties in cancer cells. The treatment of human neuroblastoma (NB) cells (SK-N-SH and LAN-1) and human ovarian cancer cells (SKOV3) with syringolin A (0,100 µm) inhibited cell proliferation in a dose-dependent manner. The IC50 (50% inhibition) for each cell line ranged between 20 µm and 25 µm. In SK-N-SH cells, the treatment with 20 µm syringolin A led to a rapid (24 h) increase of the apoptosis-associated tumour suppressor protein p53. In addition, we found that the treatment of SK-N-SH cells caused severe morphological changes after 48 h such as rounding of cells and loss of adherence, both conditions observed during apoptosis. The induction of apoptosis by syringolin A was confirmed by both poly (ADP-ribose) polymerase (PARP) cleavage and annexin V assay. Taken together, we show for the first time that the natural product syringolin A exhibits anti-proliferative activity and induces apoptosis. Syringolin A and structurally modified syringolin A derivatives may serve as new lead compounds for the development of novel anticancer drugs. [source] Insight into the Metabolism Rate of Quinone Analogues from Molecular Dynamics Simulation and 3D-QSMR MethodsCHEMICAL BIOLOGY & DRUG DESIGN, Issue 4 2007Hai-Feng Chen Molecular dynamics simulation was applied to investigate the metabolism mechanism for quinone analogues. Favourable hydrogen bonds between ligand and NQO1, and parallel orientation between ligand and flavin adenine dinucleotide could explain the difference of metabolism rate (in ,mol/min/mg) for quinone analogues. This is consistent with the experimental observation (Structure 2001;9:659,667). Then Support Vector Machines was used to construct quantitative structure,metabolism rate model. The model was evaluated by 14 test set compounds. Some descriptors selected by Support Vector Machine, were introduced into standard fields of three-dimensional quantitative structure,metabolism relationship to improve the statistical parameters of three-dimensional quantitative structure,metabolism relationship models. The results show that the inclusion of highest occupied molecular orbital and lowest unoccupied molecular orbital is meaningful for three-dimensional quantitative structure,metabolism relationship models. These in silico absorption, distribution, metabolism and excretion models are helpful in making quantitative prediction of their metabolic rates for new lead compounds before resorting in vitro and in vivo experimentation. [source] Marine Drugs , MacrolactinsCHEMISTRY & BIODIVERSITY, Issue 9 2008Xiao-Ling Lu Abstract The increasing demands for new lead compounds in pharmaceutical and agrochemical industries have driven scientists to search for new bioactive natural products. Marine microorganisms are rich sources of novel, bioactive secondary metabolites, and have attracted much attention of chemists, pharmacologists, and molecular biologists. This mini-review mainly focuses on macrolactins, a group of 24-membered lactone marine natural products, aiming at giving an overview on their sources, structures, biological activities, as well as their potential medical applications. [source] | |||||||||||||