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dc.contributor.authorBarnes, Emma C
dc.contributor.authorKumar, Rohitesh
dc.contributor.authorDavis, Rohan A
dc.date.accessioned2018-09-26T01:21:19Z
dc.date.available2018-09-26T01:21:19Z
dc.date.issued2016
dc.identifier.issn0265-0568
dc.identifier.doi10.1039/C5NP00121H
dc.identifier.urihttp://hdl.handle.net/10072/142261
dc.description.abstractA diverse range of strategies leading to natural product derived or inspired screening libraries aims to increase the number of new chemical entities emerging per year. However, the use of isolated natural products as scaffolds for the semi-synthesis of larger biological screening libraries remains rare. This particular method avoids the time-consuming and resource intensive de novo synthetic strategy for scaffold production, and has become more feasible through improvements to synthetic and isolation methodologies. This Highlight examines the increasing popularity of small- to large-sized screening libraries generated directly from isolated natural products. Several of the examples detailed herein show how this strategy can lead to improvements in not only potency but also other important (and often forgotten) drug discovery parameters such as toxicity, selectivity, lipophilicity and bioavailability. However, there are still improvements to be made to this method, particularly in the choice of the natural product scaffold and the derivatising reagents used. Avoidance of known nuisance compounds or structural alert motifs (e.g. PAINS) that interfere with bioactivity screens, and impact downstream drug development will play a significant role in the future success of this methodology. Incorporation of rational design strategies that take into account the physicochemical parameters (e.g. log P, MW, HBA, HBD) of the final semi-synthetic library analogues will also facilitate the discovery and development of leads and drugs. A multi-pronged approach to drug discovery that incorporates the use of isolated natural product scaffolds for library generation will surely be beneficial.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherRoyal Society of Chemistry
dc.relation.ispartofpagefrom372
dc.relation.ispartofpageto381
dc.relation.ispartofissue3
dc.relation.ispartofjournalNatural Product Reports
dc.relation.ispartofvolume33
dc.subject.fieldofresearchChemical sciences
dc.subject.fieldofresearchOther chemical sciences not elsewhere classified
dc.subject.fieldofresearchBiological sciences
dc.subject.fieldofresearchBiomedical and clinical sciences
dc.subject.fieldofresearchcode34
dc.subject.fieldofresearchcode349999
dc.subject.fieldofresearchcode31
dc.subject.fieldofresearchcode32
dc.titleThe use of isolated natural products as scaffolds for the generation of chemically diverse screening libraries for drug discovery
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dc.description.versionAccepted Manuscript (AM)
gro.facultyGriffith Sciences, School of Natural Sciences
gro.rights.copyright© 2016 Royal Society of Chemistry. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal website for access to the definitive, published version.
gro.hasfulltextFull Text
gro.griffith.authorDavis, Rohan A.


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