scholarly journals Cell-Based Assay Design for High-Content Screening of Drug Candidates

2016 ◽  
Vol 26 (2) ◽  
pp. 213-225 ◽  
Author(s):  
Gregory Nierode ◽  
Paul S. Kwon ◽  
Jonathan S. Dordick ◽  
Seok-Joon Kwon
Keyword(s):  
High Content Screening ◽  
Drug Candidates ◽  
Assay Design

ComfortFreezer™: A Benchtop LN2–Free Programmable Freezer for Cryopreservation of Adherent Cells in Multi-Well Plates for Cell-Based High Content Screening

2012 ◽  
Author(s):  
Matthew D. Bockman ◽  
Igor I. Katkov ◽  
Stephen B. Jones ◽  
Vsevolod Katkov ◽  
Ilya Yakhnenko
Keyword(s):  
Pluripotent Stem Cells ◽  
High Content Screening ◽  
Toxicity Tests ◽  
Neural Cells ◽  
Adherent Cells ◽  
Environmental Toxicity ◽  
Toxicity Evaluation ◽  
Drug Candidates ◽  
Large Numbers ◽  
Dissociated Cells

Human pluripotent stem cells (hPSCs) and their progeny such as hPSC-derived cardiomyocytes and neural cells hold great potential as a source for cell therapy and regenerative medicine, as well can be effectively used for high high content screening (HCS) of drug candidates and for toxicity tests. Cryopreservation (CP), storage, and shipment of the cells are key elements for eventual clinical, pharmaceutical and environmental applications, which will require large numbers of quality controlled and ready for use cells. Traditionally, the cells are frozen in suspensions of either fully dissociated cells) or loosely associated clusters such as clumps of hPSCs, clusters of beaters”of cardiomyocytes, (“or neurospheres of neural precursors. Beside logistical inconvenience for some applications such as HCS, additional manipulation with the cells (detachment, dissociation and centrifugation) can introduce substantial stress to the cells prior to freezing and after thawing, which per se may tremendously decrease the cell cryosurvival and functionality. Here, we are presenting ComfortFreezer™, a novel bench-top device specifically designed for cryopreservation in multi-well plates for cell-based high content screening (HCS), which combines a liquid-nitrogen (LN2) free programmable freezer This cryogenic equipemnt can bring serious advantage for HCS in drug screening, environmental toxicity evaluation, and other variety of HCS-based applications.

scholarly journals High-Content Screening in hPSC-Neural Progenitors Identifies Drug Candidates that Inhibit Zika Virus Infection in Fetal-like Organoids and Adult Brain

2017 ◽  
Vol 21 (2) ◽  
pp. 274-283.e5 ◽  
Author(s):  
Ting Zhou ◽  
Lei Tan ◽  
Gustav Y. Cederquist ◽  
Yujie Fan ◽  
Brigham J. Hartley ◽  
...  
Keyword(s):  
Virus Infection ◽  
Zika Virus ◽  
Neural Progenitors ◽  
Adult Brain ◽  
High Content Screening ◽  
Drug Candidates ◽  
Zika Virus Infection

RELIABILITY CRITERIA FOR SATURATION ANALYSIS OF STEROIDS BY COMPETITIVE PROTEIN BINDING

1970 ◽  
Vol 65 (1_Suppl) ◽  
pp. S61-S78 ◽  
Author(s):  
Billy D. Reeves ◽  
David W. Calhoun
Keyword(s):  
Protein Binding ◽  
Assay Method ◽  
Statistical Control ◽  
Protein Binding Assay ◽  
Competitive Protein Binding Assay ◽  
System 2 ◽  
Competitive Protein Binding ◽  
Single Method ◽  
Assay Design ◽  
Proper Perspective

ABSTRACT This communication is an attempt to delineate and define reliability criteria for saturation analysis of steroids by competitive protein binding assay. The discussion of these criteria evolved from three major considerations of assay method that help to place the ultimate criterion of accuracy in proper perspective. These major considerations are: 1) the measurement system, 2) the assay design and 3) the calculations and statistical control. Such an approach permits an evaluation, both relative and absolute, for a single method or for multiple methods.

Bringing Biocatalysis into the Deuteration Toolbox

2019 ◽  
Author(s):  
Jack Rowbotham ◽  
Oliver Lenz ◽  
Holly Reeve ◽  
Kylie Vincent
Keyword(s):  
Late Stage ◽  
Hydrogen Isotope ◽  
Reductive Amination ◽  
Mechanistic Studies ◽  
Ambient Conditions ◽  
Synthetic Pathway ◽  
Drug Candidates ◽  
Isotopic Selectivity ◽  
Reducing Equivalents

<p></p><p>Chemicals labelled with the heavy hydrogen isotope deuterium (<sup>2</sup>H) have long been used in chemical and biochemical mechanistic studies, spectroscopy, and as analytical tracers. More recently, demonstration of selectively deuterated drug candidates that exhibit advantageous pharmacological traits has spurred innovations in metal-catalysed <sup>2</sup>H insertion at targeted sites, but asymmetric deuteration remains a key challenge. Here we demonstrate an easy-to-implement biocatalytic deuteration strategy, achieving high chemo-, enantio- and isotopic selectivity, requiring only <sup>2</sup>H<sub>2</sub>O (D<sub>2</sub>O) and unlabelled dihydrogen under ambient conditions. The vast library of enzymes established for NADH-dependent C=O, C=C, and C=N bond reductions have yet to appear in the toolbox of commonly employed <sup>2</sup>H-labelling techniques due to requirements for suitable deuterated reducing equivalents. By facilitating transfer of deuterium atoms from <sup>2</sup>H<sub>2</sub>O solvent to NAD<sup>+</sup>, with H<sub>2</sub> gas as a clean reductant, we open up biocatalysis for asymmetric reductive deuteration as part of a synthetic pathway or in late stage functionalisation. We demonstrate enantioselective deuteration via ketone and alkene reductions and reductive amination, as well as exquisite chemo-control for deuteration of compounds with multiple unsaturated sites.</p><p></p>

Modular, Stereocontrolled Cβ–H/Cα–C Activation of Alkyl Carboxylic Acids

2019 ◽  
Author(s):  
Ming Shang ◽  
Karla S. Feu ◽  
Julien C. Vantourout ◽  
Lisa M. Barton ◽  
Heather L. Osswald ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Heterocyclic Compounds ◽  
Cross Coupling ◽  
Building Blocks ◽  
Enantioselective Synthesis ◽  
Carbon Centers ◽  
Drug Candidates ◽  
Rapid Diversification ◽  
Directing Group ◽  
Compound Series

<div> <div> <div> <p>The union of two powerful transformations, directed C–H activation and decarboxylative cross-coupling, for the enantioselective synthesis of vicinally functionalized alkyl, carbocyclic, and heterocyclic compounds is described. Starting from simple carboxylic acid building blocks, this modular sequence exploits the residual directing group to access more than 50 scaffolds that would be otherwise extremely difficult to prepare. The tactical use of these two transformations accomplishes a formal vicinal difunctionalization of carbon centers in a way that is modular and thus amenable to rapid diversity incorporation. A simplification of routes to known preclinical drug candidates is presented along with the rapid diversification of an antimalarial compound series. </p> </div> </div> </div>

Recent Advances in Obesity: The Role of Turmeric Tuber and Its Metabolites in the Prophylaxis and Therapeutical Strategies

2019 ◽  
Vol 25 (37) ◽  
pp. 4837-4853 ◽  
Author(s):  
Agata Jarząb ◽  
Wirginia Kukula-Koch
Keyword(s):  
Body Weight ◽  
21St Century ◽  
The Body ◽  
Excess Body Weight ◽  
Inflammatory Reactions ◽  
Drug Candidates ◽  
Scientific Papers ◽  
Important Health ◽  
High Concern

Background: Obesity in the 21st century society became an important health problem, alarming both the scientists and medicine doctors around the world. That is why, the search for new drug candidates capable to reduce the body weight is of high concern. Objective: This contribution tends to collect current findings on the biochemistry of obesity and on the application of plants and in particular turmeric tuber – a commonly used spice - as an anti-obesity agent. Methods: Following an introduction on the biochemical characteristics of obesity, the description of Curcuma secondary metabolites, their pharmacological applications and a study on the plants’ regulatory properties in obesity was summarized. Particular attention was paid to curcumin – the major metabolite present in the extracts of Curcuma spp., which is known to exhibit a variety of pharmacological actions. Also, the characteristics of some semisynthetic analogues of this ferulic acid derivative, characterized by a higher polarity and better bioavailability will be discussed. Results: Numerous scientific papers treat on the influence of turmeric on weight loss. Additionally, some of them describe its anti-inflammatory properties. Conclusions: This important spice tends to fight the 21st century plague, which is an excessive weight gain, related to the development of metabolic syndrome, to the occurrence of cardiovascular problems and diabetes, and, in consequence, leading to a significant shortening of life span. As herein proven, the extracts of turmeric play an important role in the regulation of inflammatory reactions which are evoked in the overweight patients, helping them reduce the excess body weight.

Antitubercular Marine Natural Products

2018 ◽  
Vol 25 (20) ◽  
pp. 2304-2328 ◽  
Author(s):  
Lishu Wang ◽  
Jungfeng Wang ◽  
Juan Liu ◽  
Yonghong Liu
Keyword(s):  
Natural Products ◽  
Marine Natural Products ◽  
Antitubercular Activity ◽  
Marine Resources ◽  
Drug Candidates ◽  
New Drug ◽  
Chemical Constitution

Due to the importance of nature as a source of new drug candidates, the purpose of this article is to emphasize the marine natural products, which exhibit antitubercular activity, published between January 2000 and May 2016, with 138 quotations to 250 compounds obtained from marine resources. These metabolites are organized by chemical constitution and named as simple alkyl lipids derivatives, aromatics derivatives, peptides, alkaloids, terpenoids, steroids, macrolides, and polycyclic polyketides.

Recent Advances in the Development of Antimicrobial Peptides (AMPs): Attempts for Sustainable Medicine?

2018 ◽  
Vol 25 (21) ◽  
pp. 2503-2519 ◽  
Author(s):  
Anne Kokel ◽  
Marianna Torok
Keyword(s):  
Side Effects ◽  
Antimicrobial Peptides ◽  
Potential Drug ◽  
Green Technologies ◽  
Specific Antibodies ◽  
Structural Modifications ◽  
Drug Candidates ◽  
Induce Resistance ◽  
Conventional Antibiotics

Background: Since the first isolation of antimicrobial peptides (AMPs) they have attracted extensive interest in medicinal chemistry. However, only a few AMP-based drugs are currently available on the market. Despite their effectiveness, biodegradability, and versatile mode of action that is less likely to induce resistance compared to conventional antibiotics, AMPs suffer from major issues that need to be addressed to broaden their use. Notably, AMPs can lack selectivity leading to side effects and cytotoxicity, and also exhibit in vivo instability. Several strategies are being actively considered to overcome the limitations that restrain the success of AMPs. Methods: In the current work, recent strategies reported for improving AMPs in the context of drug design and delivery were surveyed, and also their possible impact on patients and the environment was assessed. Results: As a major advantage AMPs possess an easily tunable skeleton offering opportunities to improve their properties. Strategic structural modifications and the beneficial properties of cyclic or branched AMPs in term of stability have been reported. The conjugation of AMPs with nanoparticles has also been explored to increase their in vivo stability. Other techniques such as the coupling of AMPs with specific antibodies aim to increase the selectivity of the potential drug towards the target. These strategies were evaluated for their effect on the environment highlighting green technologies. Conclusion: Although further research is needed taking into account both environmental and human health consequences of novel AMPs, several of these compounds are promising drug candidates for use in sustainable medicine.

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