The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
High-Throughput Method for the Production and Analysis of Large Natural Product Libraries for Drug Discovery
Abstract
High-throughput methods were applied to the production, analysis, and characterization of libraries of natural products in order to accelerate the drug discovery process for high-throughput screening in the pharmaceutical and biotechnology industries. Library production integrates automated flash chromatography, solid-phase extraction, filtration, and high-throughput parallel four-channel preparative high-performance liquid chromatography to obtain the libraries in 96- or 384-well plates. Libraries consist of purified fractions with approximately one to five compounds per well. Libraries are analyzed prior to biological screening by a high-throughput parallel eight-channel liquid chromatography-evaporative light scattering detection-mass spectrometry system to determine the molecular weight, number, and quantity of compounds in a fraction. After biological screening, active fractions are rapidly purified at the microgram level and individual compounds are rescreened for confirmation of activity. Structures of active compounds are elucidated by NMR spectroscopy and mass spectrometry. Utilization of a novel microcoil probe allows NMR data to be gathered on 50 microg. As a demonstration, a library was made from the stem bark of Taxus brevifolia. Biological screening in the National Cancer Institute's in vitro panel of three cancer cell lines demonstrates that the process enables the discovery of active anticancer compounds not detected in the flash fractions from which the library originates.
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The role of natural product chemistry in drug discovery
Butler, M. S. (2004) · Journal of Natural Products · doi:10.1021/np040106y · Cited by 1,381
Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery
Thomford, N. E., Senthebane, D. A., Rowe, A., Munro, D., Seele, P., Maroyi, A., & Dzobo, K. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19061578 · Cited by 1,241
The pharmaceutical industry and natural products: historical status and new trends
David, B., Wolfender, J.-L., & Dias, D. A. (2015) · Phytochemistry Reviews · doi:10.1007/s11101-014-9367-z · Cited by 579
New aspects of natural products in drug discovery
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Plant natural products: Back to the future or into extinction?
McChesney, J. D., Venkataraman, S. K., & Henri, J. T. (2007) · Phytochemistry · doi:10.1016/j.phytochem.2007.04.032 · Cited by 377
The Tox21 10K Compound Library: Collaborative Chemistry Advancing Toxicology
Richard, A. M., Huang, R., Waidyanatha, S., Shinn, P., Collins, B. J., Thillainadarajah, I., Grulke, C. M., Williams, A. J., Lougee, R. R., Judson, R. S., et al. (2021) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.0c00264 · Cited by 323
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Natural Products as a Foundation for Drug Discovery
Beutler, J. A. (2009) · Current Protocols in Pharmacology · doi:10.1002/0471141755.ph0911s46 · Cited by 296
Metadata
- Authors
- Eldridge, G. R., Vervoort, H. C., Lee, C. M., Cremin, P. A., Williams, C. T., Hart, S. M., Goering, M. G., O'Neil-Johnso, M., & Zeng, L.
- Venue
- Analytical Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2002-07-18
- Volume
- 74
- Issue
- 16
- Pages
- 3963-3971
- ISSN
- 0003-2700 (ISSN-L)
- 1520-6882
- OpenAlex
- W1968903040
- Cited by
- 258
- References
- 8
- FWCI
- 17.29
- Type
- journal article
- Language
- en
- Open access
- closed
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