High-Throughput, Microarray-Based Synthesis of Natural Product Analogues via in Vitro Metabolic Pathway Construction

2007 ◽  
Vol 2 (6) ◽  
pp. 419-425 ◽  
Author(s):  
Seok Joon Kwon ◽  
Moo-Yeal Lee ◽  
Bosung Ku ◽  
David H. Sherman ◽  
Jonathan S. Dordick
Keyword(s):  
Natural Product ◽  
High Throughput ◽  
Metabolic Pathway

High-Throughput Screening Platform for the Discovery of New Immunomodulator Molecules from Natural Product Extract Libraries

2016 ◽  
Vol 21 (6) ◽  
pp. 567-578 ◽  
Author(s):  
José Pérez del Palacio ◽  
Caridad Díaz ◽  
Mercedes de la Cruz ◽  
Frederick Annang ◽  
Jesús Martín ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Natural Product ◽  
High Throughput ◽  
High Throughput Screening ◽  
Viral Infections ◽  
Inflammatory Diseases ◽  
Immunomodulatory Activity ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

It is widely accepted that central nervous system inflammation and systemic inflammation play a significant role in the progression of chronic neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease, neurotropic viral infections, stroke, paraneoplastic disorders, traumatic brain injury, and multiple sclerosis. Therefore, it seems reasonable to propose that the use of anti-inflammatory drugs might diminish the cumulative effects of inflammation. Indeed, some epidemiological studies suggest that sustained use of anti-inflammatory drugs may prevent or slow down the progression of neurodegenerative diseases. However, the anti-inflammatory drugs and biologics used clinically have the disadvantage of causing side effects and a high cost of treatment. Alternatively, natural products offer great potential for the identification and development of bioactive lead compounds into drugs for treating inflammatory diseases with an improved safety profile. In this work, we present a validated high-throughput screening approach in 96-well plate format for the discovery of new molecules with anti-inflammatory/immunomodulatory activity. The in vitro models are based on the quantitation of nitrite levels in RAW264.7 murine macrophages and interleukin-8 in Caco-2 cells. We have used this platform in a pilot project to screen a subset of 5976 noncytotoxic crude microbial extracts from the MEDINA microbial natural product collection. To our knowledge, this is the first report on an high-throughput screening of microbial natural product extracts for the discovery of immunomodulators.

scholarly journals High-throughput screening identifies a novel natural product-inspired scaffold capable of inhibiting Clostridioides difficile in vitro

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rusha Pal ◽  
Mingji Dai ◽  
Mohamed N. Seleem
Keyword(s):  
Natural Product ◽  
High Throughput ◽  
High Throughput Screening ◽  
Pseudomembranous Colitis ◽  
Standard Of Care ◽  
Watery Diarrhea ◽  
Microbial Dysbiosis ◽  
Clostridioides Difficile ◽  
In Vitro Investigation

AbstractClostridioides difficile is an enteric pathogen responsible for causing debilitating diarrhea, mostly in hospitalized patients. The bacterium exploits on microbial dysbiosis induced by the use of antibiotics to establish infection that ranges from mild watery diarrhea to pseudomembranous colitis. The increased prevalence of the disease accompanied by exacerbated comorbidity and the paucity of anticlostridial drugs that can tackle recurrence entails novel therapeutic options. Here, we report new lead molecules with potent anticlostridial activity from the AnalytiCon NATx library featuring natural product-inspired or natural product-derived small molecules. A high-throughput whole-cell-based screening of 5000 synthetic compounds from the AnalytiCon NATx library helped us identify 10 compounds capable of inhibiting the pathogen. Out of these 10 hits, we found 3 compounds with potent activity against C. difficile (MIC = 0.5–2 μg/ml). Interestingly, these compounds had minimal to no effect on the indigenous intestinal microbial species tested, unlike the standard-of-care antibiotics vancomycin and fidaxomicin. Further in vitro investigation revealed that the compounds were nontoxic to Caco-2 cell line. Given their potent anticlostridial activity, natural product-inspired scaffolds may suggest potential avenues that can address the unmet needs in preventing C. difficile mediated disease.

scholarly journals Novel In Vitro Protein Fragment Complementation Assay Applicable to High-Throughput Screening in a 1536-Well Format

2009 ◽  
Vol 14 (8) ◽  
pp. 970-979 ◽  
Author(s):  
Junko Hashimoto ◽  
Taku Watanabe ◽  
Tatsuya Seki ◽  
Satoshi Karasawa ◽  
Miho Izumikawa ◽  
...  
Keyword(s):  
Natural Product ◽  
High Throughput ◽  
High Throughput Screening ◽  
Protein Fragment ◽  
Complementation Assay ◽  
Protein Fragment Complementation ◽  
Natural Product Library ◽  
Protein Fragment Complementation Assay ◽  
Vitro Protein

Protein-protein interactions (PPIs) play key roles in all cellular processes and hence are useful as potential targets for new drug development. To facilitate the screening of PPI inhibitors as anticancer drugs, the authors have developed a high-throughput screening (HTS) system using an in vitro protein fragment complementation assay (PCA) with monomeric Kusabira-Green fluorescent protein (mKG). The in vitro PCA system was established by the topological formation of a functional complex between 2 split inactive mKG fragments fused to target proteins, which fluoresces when 2 target proteins interact to allow complementation of the mKG fragments. Using this assay system, the authors screened inhibitors for TCF7/β-catenin, PAC1/PAC2, and PAC3 homodimer PPIs from 123,599 samples in their natural product library. Compound TB1 was identified as a specific inhibitor for PPI of PAC3 homodimer. TB1 strongly inhibited the PPI of PAC3 homodimer with an IC 50 value of 0.020 µM and did not inhibit PPI between TCF7/β-catenin and PAC1/PAC2 even at a concentration of 250 µM. The authors thus demonstrated that this in vitro PCA system applicable to HTS in a 1536-well format is capable of screening for PPI inhibitors from a huge natural product library. ( Journal of Biomolecular Screening 2009:970-979)

New Antileishmanial Drug Leads from a Library of Natural Product Fractions Prepared by a High Throughput Fractionation Paradigm*

Planta Medica ◽  
2012 ◽  
Vol 78 (05) ◽  
Author(s):  
SK Jain ◽  
R Sahu ◽  
J Zhang ◽  
MR Jacob ◽  
XC Li ◽  
...  
Keyword(s):  
Natural Product ◽  
High Throughput ◽  
Antileishmanial Drug ◽  
Drug Leads

High throughput huaman pancreactic lipase screening of natural product library for lipase inhibition activity

Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
P Jiao ◽  
J Zhao ◽  
J Yeop Lee ◽  
J Tseng-Crank ◽  
B Corneliusen ◽  
...  
Keyword(s):  
Natural Product ◽  
High Throughput ◽  
Inhibition Activity ◽  
Natural Product Library ◽  
Lipase Screening ◽  
Lipase Inhibition

New Imidazole Inhibitors of Mycobacterial FtsZ: the Way from High-Throughput Molecular Screening in Grid up to in vitro Verification

2016 ◽  
Vol 12 (3) ◽  
pp. 43-55 ◽  
Author(s):  
P.A. Karpov ◽  
◽  
O.M. Demchuk ◽  
V.M. Britsun ◽  
D.I. Lytvyn ◽  
...  
Keyword(s):  
High Throughput ◽  
Molecular Screening ◽  
The Way
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