Investigation of a New Family of Chiral Ligands for Enantioselective Catalysis via Parallel Synthesis and High-Throughput Screening

1998 ◽  
Vol 63 (16) ◽  
pp. 5312-5313 ◽  
Author(s):  
Cesare Gennari ◽  
Simona Ceccarelli ◽  
Umberto Piarulli ◽  
Christian A. G. N. Montalbetti ◽  
Richard F. W. Jackson
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Parallel Synthesis ◽  
Chiral Ligands ◽  
Enantioselective Catalysis ◽  
New Family

ChemInform Abstract: Investigation of a New Family of Chiral Ligands for Enantioselective Catalysis via Parallel Synthesis and High-Throughput Screening.

ChemInform ◽  
2010 ◽  
Vol 30 (1) ◽  
pp. no-no
Author(s):  
C. GENNARI ◽  
S. CECCARELLI ◽  
U. PIARULLI ◽  
C. A. G. N. MONTALBETTI ◽  
R. F. W. JACKSON
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Parallel Synthesis ◽  
Chiral Ligands ◽  
Enantioselective Catalysis ◽  
New Family

scholarly journals High-throughput phenotypic screen identifies a new family of potent anti-amoebic compounds

2021 ◽  
Author(s):  
Conall Sauvey ◽  
Gretchen Ehrenkaufer ◽  
Jonathan Blevitt ◽  
Paul Jackson ◽  
Ruben Abagyan
Keyword(s):  
Entamoeba Histolytica ◽  
High Throughput ◽  
High Throughput Screening ◽  
Large Scale ◽  
Life Stage ◽  
Current Standard ◽  
New Family ◽  
Entamoeba Invadens ◽  
Related Compounds

AbstractEntamoeba histolytica is a disease-causing parasitic amoeba which affects an estimated 50 million people worldwide, particularly in socioeconomically vulnerable populations experiencing water sanitation issues. Infection with E. histolytica is referred to as amoebiasis, and can cause symptoms such as colitis, dysentery, and even death in extreme cases. Drugs exist that are capable of killing this parasite, but they are hampered by downsides such as significant adverse effects at therapeutic concentrations, issues with patient compliance, the need for additional drugs to kill the transmissible cyst stage, and potential development of resistance. Past screens of small and medium sized chemical libraries have yielded anti-amoebic candidates, thus rendering high-throughput screening a promising direction for new drug discovery in this area. In this study, we screened a curated 80,000-compound library from Janssen pharmaceuticals against E. histolytica trophozoites in vitro, and from it identified a highly potent new inhibitor compound. Further experimentation confirmed the activity of this compound, as well as that of several structurally related compounds, originating from both the Janssen Jump-stARter library, and from chemical vendors, thus highlighting a new structure-activity relationship (SAR). In addition, we confirmed that the compound inhibited E. histolytica survival as rapidly as the current standard of care and inhibited transmissible cysts of the related model organism Entamoeba invadens. Together these results constitute the discovery of a novel class of chemicals with favorable in vitro pharmacological properties which may lead to an improved therapy against this parasite and in all of its life stages.Author summaryThe parasite Entamoeba histolytica represents a significant challenge in the field of global health. It currently infects and causes disease among millions of people worldwide, particularly those lacking access to clean water. Drugs exist to treat this disease, but nevertheless it persists as a problem, likely at least partly due to problems and downsides inherent to these drugs. Hence the search for new and better ones is needed. We report here our contribution to this search, consisting of testing a large, carefully-curated collection of tens of thousands of chemicals for their ability to kill E. histolytica. This large-scale test resulted in the identification of one of the compounds as potently anti-amoebic, capable of killing the parasite cells at extremely low concentrations. Further experimentation found several chemically-related compounds to also possess this property, and additionally found the first compound capable of killing the infective life stage of another Entamoeba parasite. These results have revealed an entire new family of chemicals with good potential for development as better drugs against this disease.

High Throughput Synthesis of Pigments by Solution Deposition

2004 ◽  
Vol 848 ◽  
Author(s):  
Stuart J. Henderson ◽  
Andrew L. Hector ◽  
Mark T. Weller
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Parallel Synthesis ◽  
Inorganic Materials ◽  
X Ray Diffraction ◽  
Solution Deposition ◽  
X Ray ◽  
Effective Strategies ◽  
Simultaneous Synthesis ◽  
Composition Structure

ABSTRACTCombinatorial and high throughput methods have been utilised in the pharmaceutical industry for many years. The process involves the simultaneous synthesis of libraries containing thousands of compounds, which can then be screened for desirable properties. More recently the concepts of parallel synthesis and high-throughput screening have emerged as effective strategies in the search for novel inorganic materials. We report the development of high throughput methods, which have been used for the synthesis and preliminary characterisation of ceramic oxide pigments on an alumina substrate. This methodology has been utilised to prepare compounds with the spinel structure in the series Cu1-xZnxAl2-yCryO4 (0≤x≤1, 0≤y≤2) at a range of temperatures. The materials are analysed by rapid sequential X-ray diffraction and a simple colour measurement technique. The optical properties across the quaternary landscape can therefore be mapped as a function of composition, structure and annealing temperature.

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