Faculty Opinions recommendation of Discovery of New Compounds Active against Plasmodium falciparum by High Throughput Screening of Microbial Natural Products.

2016 ◽  
Author(s):  
Audrey Odom John
Keyword(s):  
Plasmodium Falciparum ◽  
Natural Products ◽  
High Throughput ◽  
High Throughput Screening ◽  
New Compounds ◽  
Microbial Natural Products

scholarly journals Discovery of New Compounds Active against Plasmodium falciparum by High Throughput Screening of Microbial Natural Products

PLoS ONE ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. e0145812 ◽  
Author(s):  
Guiomar Pérez-Moreno ◽  
Juan Cantizani ◽  
Paula Sánchez-Carrasco ◽  
Luis Miguel Ruiz-Pérez ◽  
Jesús Martín ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Natural Products ◽  
High Throughput ◽  
High Throughput Screening ◽  
New Compounds ◽  
Microbial Natural Products

scholarly journals New Approach for High-Throughput Screening of Drug Activity on Plasmodium Liver Stages

2006 ◽  
Vol 50 (4) ◽  
pp. 1586-1589 ◽  
Author(s):  
Audrey Gego ◽  
Olivier Silvie ◽  
Jean-François Franetich ◽  
Khemaïs Farhati ◽  
Laurent Hannoun ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
High Throughput ◽  
High Throughput Screening ◽  
Scanning System ◽  
New Approach ◽  
Drug Activity ◽  
Hepatic Cells ◽  
High Throughput Drug Screening ◽  
Prophylactic Drugs

ABSTRACT Plasmodium liver stages represent potential targets for antimalarial prophylactic drugs. Nevertheless, there is a lack of molecules active on these stages. We have now developed a new approach for the high-throughput screening of drug activity on Plasmodium liver stages in vitro, based on an infrared fluorescence scanning system. This method allowed us to count automatically and rapidly Plasmodium-infected hepatocytes, using different hepatic cells and different Plasmodium species, including Plasmodium falciparum. This new technique is well adapted for high-throughput drug screening and should facilitate the identification of new antimalarial compounds active on Plasmodium liver stages.

scholarly journals High throughput screening of natural products for LDH inhibition as an anti‐mitotic therapeutic target (585.3)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Shihab Deiab ◽  
Elizabeth Mazzio ◽  
Najla Zarmouh ◽  
Nzinga Mack ◽  
Karam Soliman
Keyword(s):  
Natural Products ◽  
High Throughput ◽  
Therapeutic Target ◽  
High Throughput Screening

scholarly journals A biotechnological approach for the development of new antifungal compounds to protect the environment and the human health

2015 ◽  
Vol 4 (3) ◽  
Author(s):  
Claudia Zani ◽  
Francesco Maria Restivo ◽  
Mauro Carcelli ◽  
Donatella Feretti ◽  
Giorgio Pelosi ◽  
...  
Keyword(s):  
Human Health ◽  
High Throughput ◽  
High Throughput Screening ◽  
Animal Feed ◽  
Po Valley ◽  
Biotechnological Approach ◽  
Relevant Role ◽  
Food Economy ◽  
Set Up ◽  
New Compounds

<em>Background</em>. In the Po Valley aflatoxins play a relevant role: the local food economy is heavily based on cereal cultivations for animal feed and human nutrition. Aims of this project are the identification of new compounds that inhibit <em>Aspergillus</em> proliferation, the development of new inhibitors of aflatoxins production, and the set-up a practical screening procedure to identify the most effective and safe compounds. <br /><em>Design and Methods.</em> New compounds will be synthetized with natural origin molecules as ligands and endogenous metal ions to increase their bioavailability for the fungi as metal complexes. A biotechnological high-throughput screening will be set up to identify efficiently the most powerful substances. The newly synthesized compounds with effective antifungal activities, will be evaluated with battery of tests with different end-points to assess the toxic potential risk for environmental and human health. <br /><em>Expected impact of the study for public health.</em> The fundamental step in the project will be the synthesis of new compounds and the study of their capability to inhibit aflatoxin biosynthesis. A new, simple, inexpensive and high-throughput method to screen the anti-fungine and anti-mycotoxin activity of the new synthesised compounds will be applied. The evaluation of possible risks for humans due to toxic and genotoxic activities of the molecules will be made with a new approach using different types of cells (bacteria, plants and human cells).

High throughput screening to identify new compounds with proapoptotic activity in resistant lung cancer cells

2015 ◽  
Vol 32 (3) ◽  
pp. 324
Author(s):  
P. Gilson ◽  
L. Vanwonterghem ◽  
F. Mahuteau ◽  
S. Piguel ◽  
J.L. Coll ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
High Throughput ◽  
High Throughput Screening ◽  
Lung Cancer Cells ◽  
New Compounds

scholarly journals High-throughput Screening for Potent and Selective Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase

2005 ◽  
Vol 280 (23) ◽  
pp. 21847-21853 ◽  
Author(s):  
Jeffrey Baldwin ◽  
Carolyn H. Michnoff ◽  
Nicholas A. Malmquist ◽  
John White ◽  
Michael G. Roth ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Binding Site ◽  
High Throughput ◽  
High Throughput Screening ◽  
De Novo ◽  
Site Directed Mutagenesis ◽  
Structural Basis ◽  
Dihydroorotate Dehydrogenase ◽  
Selective Inhibitors ◽  
Diverse Range

Plasmodium falciparum is the causative agent of the most serious and fatal malarial infections, and it has developed resistance to commonly employed chemotherapeutics. The de novo pyrimidine biosynthesis enzymes offer potential as targets for drug design, because, unlike the host, the parasite does not have pyrimidine salvage pathways. Dihydroorotate dehydrogenase (DHODH) is a flavin-dependent mitochondrial enzyme that catalyzes the fourth reaction in this essential pathway. Coenzyme Q (CoQ) is utilized as the oxidant. Potent and species-selective inhibitors of malarial DHODH were identified by high-throughput screening of a chemical library, which contained 220,000 drug-like molecules. These novel inhibitors represent a diverse range of chemical scaffolds, including a series of halogenated phenyl benzamide/naphthamides and urea-based compounds containing napthyl or quinolinyl substituents. Inhibitors in these classes with IC50 values below 600 nm were purified by high pressure liquid chromatography, characterized by mass spectroscopy, and subjected to kinetic analysis against the parasite and human enzymes. The most active compound is a competitive inhibitor of CoQ with an IC50 against malarial DHODH of 16 nm, and it is 12,500-fold less active against the human enzyme. Site-directed mutagenesis of residues in the CoQ-binding site significantly reduced inhibitor potency. The structural basis for the species selective enzyme inhibition is explained by the variable amino acid sequence in this binding site, making DHODH a particularly strong candidate for the development of new anti-malarial compounds.

scholarly journals High-Throughput Screening Platform for Natural Product–Based Drug Discovery Against 3 Neglected Tropical Diseases

2014 ◽  
Vol 20 (1) ◽  
pp. 82-91 ◽  
Author(s):  
F. Annang ◽  
G. Pérez-Moreno ◽  
R. García-Hernández ◽  
C. Cordon-Obras ◽  
J. Martín ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Natural Product ◽  
High Throughput ◽  
High Throughput Screening ◽  
Neglected Tropical Diseases ◽  
Chemical Diversity ◽  
Tropical Diseases ◽  
Isolation And Characterization ◽  
Microbial Extracts

African trypanosomiasis, leishmaniasis, and Chagas disease are 3 neglected tropical diseases for which current therapeutic interventions are inadequate or toxic. There is an urgent need to find new lead compounds against these diseases. Most drug discovery strategies rely on high-throughput screening (HTS) of synthetic chemical libraries using phenotypic and target-based approaches. Combinatorial chemistry libraries contain hundreds of thousands of compounds; however, they lack the structural diversity required to find entirely novel chemotypes. Natural products, in contrast, are a highly underexplored pool of unique chemical diversity that can serve as excellent templates for the synthesis of novel, biologically active molecules. We report here a validated HTS platform for the screening of microbial extracts against the 3 diseases. We have used this platform in a pilot project to screen a subset (5976) of microbial extracts from the MEDINA Natural Products library. Tandem liquid chromatography–mass spectrometry showed that 48 extracts contain potentially new compounds that are currently undergoing de-replication for future isolation and characterization. Known active components included actinomycin D, bafilomycin B1, chromomycin A3, echinomycin, hygrolidin, and nonactins, among others. The report here is, to our knowledge, the first HTS of microbial natural product extracts against the above-mentioned kinetoplastid parasites.

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